Risk Prediction of Post-Endoscopic Submucosal Dissection Coagulation Syndrome.

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been popular worldwide to treat laterally spreading tumors and large polyps. Post-ESD coagulation syndrome (PECS) is more common than the two major ESD-related complications, perforation, and bleeding. The aim of this study was to assess the prevalence of PECS, identify the risk factors for PECS, and create a risk prediction model for PECS. METHODS: Retrospective cross-sectional study analyzed a total of 986 patients who underwent colorectal ESD. Logistic regression models were used to assess risk factors with PECS. Each risk factor was scored, and the 3-step risk stratification index of prediction model was assessed. RESULTS: The prevalence of PECS was 21.4% (95% confidence interval [CI] = 18.9-24.1%). The risk factors of PECS in the multivariate logistic regression were tumor size (+1 cm: odds ratio [OR], 1.29; 95% CI, 1.16-7.09), cecal lesion (OR, 1.96; 95% CI, 1.09-1.53), procedure time (+30 min: OR, 1.19; 95% CI, 1.02-1.39), and ESD with snaring (OR, 0.64; 95% CI, 0.43-0.95). Applying a simplified weighted scoring system based on adjusted OR increments of 1, the risk of PECS was 12.3% (95% CI, 0.3-16.0%) for the low-risk group (score ≤4) and was 36.0% (95% CI = 29.4-43.2%) for the high-risk group (score ≥8). Overall discrimination (C-statistic = 0.629; 95% CI = 0.585-0.672) and calibration (p = 0.993) of the model were moderate to good. CONCLUSION: PECS occurs frequently, and the prediction model can be helpful for effective treatment and prevention of PECS.

Clinicopathologic and Endosonographic Characteristics of Colon Subepithelial Tumors Discovered Incidentally.

BACKGROUND/AIMS: Colonoscopy is commonly used for colorectal cancer screening; therefore, the detection of colon subepithelial tumors (SETs) has also increased. Several research studies have been undertaken to diagnose and treat stomach and rectal SETs. The purpose of this study was to determine a diagnostic point for colon SETs by comparing histological findings with the endoscopic characteristics of colon SETs discovered by chance. METHODS: A total 194 patients underwent an endoscopic ultrasound (EUS) for suspicious colon SETs during a colonoscopy from May 2014 to December 2021. A total of 105 colon SETs, which were histologically diagnosed, were finally included. Fisher's exact test was used to determine the factors associated with malignant SETs. RESULTS: Colon SETs were predominantly present in the right colon (n = 73, 69.5%), particularly in the transverse colon (n = 32, 30.5%). The majority were smaller than 10 mm (n = 88, 83.8%), and they had hard consistencies (n = 84, 80%) and exhibited no surface changes (n = 96, 91.4%). Most of them were found in the submucosal layers (n = 54, 51.4%) and had a hypoechoic pattern (n = 56, 53.3%) in the EUS. Of the histologically confirmed cases, only three (3/105, 2.9%) were malignant. Most benign lesions were lipomas, suspected parasitic infections, or lesions caused by various inflammatory reactions, including fibrous/fibrocalcific lesions and necrotic nodules. All soft lesions were benign. Two of the three malignant lesions were adenocarcinomas, and the other was lymphoma. For the malignant SETs, there was a statistically significant alteration in the surface of the tumors (p < 0.001), and they were located where the muscularis mucosa layer was included (p = 0.008). The potential malignant SETs, granular cell tumors, and neuroendocrine tumors (NETs) had similar features, such as yellowish hypoechoic masses. Colon NETs were only found in the rectosigmoid junction. Parasitic infections and lesions, resulting in various inflammatory reactions, were observed as pale and hard SETs and mostly revealed as mixed echogenic masses located in the muscularis mucosa, submucosa, or multi-layers in the EUS. CONCLUSION: This study showed that small colon SETs were mostly benign lesions. Despite its rarity, pathological confirmation is crucial in cases where the SET has surface changes and has been located in a position where the muscularis mucosa layer was included on the EUS, due to the risk of malignancy.

Risk factors and management of iatrogenic colorectal perforation in diagnostic colonoscopy: a single-center cohort study.

BACKGROUND AND AIMS: Diagnostic colonoscopy plays a central role in colorectal cancer screening programs. We analyzed the risk factors for perforation during diagnostic colonoscopy and discussed the treatment outcomes. METHODS: We performed a retrospective analysis of risk factors and treatment outcomes of perforation during 74,426 diagnostic colonoscopies between 2013 and 2018 in a tertiary hospital. RESULTS: A total of 19 perforations were identified after 74,426 diagnostic colonoscopies or sigmoidoscopies, resulting in a standardized incidence rate of 0.025% or 2.5 per 10,000 colonoscopies. The majority (15 out of 19, 79%) were found at the sigmoid colon and recto-sigmoid junction. Perforation occurred mostly in less than 1000 cases of colonoscopy (16 out of 19, 84%). In particular, the incidence of perforation was higher in more than 200 cases undergoing slightly advanced colonoscopy rather than beginners who had just learned colonoscopy. Old age (≥ 70 years), inpatient setting, low body mass index (BMI), and sedation status were significantly associated with increased risk of perforation. Nine (47%) of the patients underwent operative treatment and ten (53%) were managed non-operatively. Patients who underwent surgery were often diagnosed with delayed or concomitant abdominal pain. Perforations of rectum tended to be successfully treated with endoscopic clipping. CONCLUSIONS: Additional precautions are required to prevent perforation in elderly patients, hospital settings, low BMI, sedated patients, or by a doctor with slight familiarity with endoscopies (but still insufficient experience). Endoscopic treatment should be actively considered if diagnosis is prompt, abdominal pain absent, and especially the rectal perforation is present.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea.

BACKGROUND: The incidence of colorectal cancer (CRC) and preinvasive CRC (e.g., early colon cancer and advanced adenoma) is gradually increasing in several countries. AIM: To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea. METHODS: This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC, and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies. Colonoscopy-related complications by age group were also determined. RESULTS: The incidence of CRC showed a rapid increase, then decreased after 2012 in the 50-75 year-age group. During the study period, the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age. Since 2009, the increase has been rapid, showing a pattern similar to the increase in colonoscopies. The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007. The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age. CONCLUSION: The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed. As the risk of colonoscopy-related hospitalization and death is high in the elderly, if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75, colonoscopy-related complications can be reduced for those aged 76 years or over.

Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn's Disease.

Background/Aims: The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison to balloon-assisted enteroscopy (BAE) for patients with small bowel Crohn's disease (CD). We studied the correlation of MARIAs with simple endoscopic scores for CD (SES-CD) of the ileum based on magnetic resonance enterography (MRE) and BAE in patients with small bowel CD. Methods: Fifty patients with small bowel CD who underwent BAE and MRE concurrently within 3 months from September 2020 to June 2021 were enrolled in the study. The primary outcome was the correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE. The cutoff value for MARIAs identifying endoscopically active/severe disease, defined as ileal SES-CDa/ileal SES-CD of 5/7 or more, was analyzed. Results: Ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001; R=0.78, p<0.001). The area under the receiver operating characteristic curve of MARIAs for ileal SES-CDa ≥5 and ileal SES-CD ≥7 was 0.92 (95% confidence interval, 0.88 to 0.97) and 0.92 (95% confidence interval, 0.87 to 0.97). The cutoff value of MARIAs for detecting active/severe disease was 3. A MARIAs index value of ≥3 identified ileal SES-CDa ≥5 with a sensitivity of 85% and specificity of 87% and detected ileal SES-CD ≥7 with a sensitivity of 87% and specificity of 86%. Conclusions: This study validated the applicability of MARIAs compared to BAE-based ileal SES-CDa/SES-CD.

Weight loss from diagnosis of Crohn's disease to one year post-diagnosis results in earlier surgery.

Malnutrition might play a key role in the prognosis of patients with Crohn's disease (CD). The aim of this study was to explore the impact of weight loss from diagnosis of CD to one-year post-diagnosis on disease prognosis in terms of surgery. Patients who were diagnosed with CD at Samsung Medical Center between 1995 to 2020 were included in this study. The study defined the "group with weight loss" as patients with weight loss in one year after diagnosis and the "group without body weight loss" as patients without weight loss in one year after diagnosis. Their data such as demographics, laboratory findings, and medical interventions were collected retrospectively. The primary outcome was confirmation of the difference in the incidence of surgery associated with CD between the group with weight loss and the group without body weight loss. We further analyzed factors associated with surgery outcomes. A total of 165 patients were analyzed in this study. Forty-one patients (24.8%) had body weight loss whereas 124 patients (75.2%) had no body weight loss. Body change at one year showed no significant association with direct surgical incidence. However, the patients with weight loss tended to undergo surgery earlier than patients without body weight loss. Among factors associated with outcomes of Crohn's surgery, the albumin was the only significant factor. Patients with weight loss had no statistically significant increase in the risk of surgery than patients without weight loss, although they tended to undergo surgery earlier than patients without body weight loss. A prospective study is needed to determine serial body weight changes during follow-up for patients with CD.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn's disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn's disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn's disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0-6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0-6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48-26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with "cannot be passed" compared to the cases without stenosis (HR 12.34; 95% CI 1.66-91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

The optimal surgery timing after stenting in colorectal cancer patients with malignant obstruction: additionally compared with emergency surgery.

BACKGROUND: This study aimed to determine short-term and long-term outcomes according to time intervals after stenting and compared them with those of emergency surgery (ES) in colorectal cancer (CRC) with malignant obstruction. METHODS: CRC with malignant obstructions was reviewed retrospectively between January 2008 and July 2018. Of a total of 539 patients who visited the emergency room and underwent ES, 133 were enrolled in the ES group. Of a total of 567 patients who initially received stenting and subsequently underwent elective surgery, 220 were enrolled in the SEMS group. The interval between SEMS placement and elective surgery was classified as < 11 days, 11-17 days, and > 17 days. RESULTS: For those who received SEMS (n = 220), those with a time interval of 11-17 days (n = 97) had fewer hospital days than those with a time interval of < 11 days (n = 68) (8 days vs. 15 days) and less stoma formation than those with a time interval of > 17 days (n = 55) (1.0% vs. 14.6%). Multivariable analysis revealed a decreased risk of death for the group with a time interval of 11-17 days (20.6%) compared to the ES group (31.6%) (hazard ratio: 0.48; 95% confidence interval: 0.24-0.97). Disease-free survival was comparable between the SEMS and ES groups regardless of the time interval (log-rank p = 0.52). CONCLUSIONS: The time interval of 11-17 days after stenting to elective surgery appeared to be associated with the most favorable outcomes.

Deep learning model for distinguishing Mayo endoscopic subscore 0 and 1 in patients with ulcerative colitis.

The aim of this study was to address the issue of differentiating between Mayo endoscopic subscore (MES) 0 and MES 1 using a deep learning model. A dataset of 492 ulcerative colitis (UC) patients who demonstrated MES improvement between January 2018 and December 2019 at Samsung Medical Center was utilized. Specifically, two representative images of the colon and rectum were selected from each patient, resulting in a total of 984 images for analysis. The deep learning model utilized in this study consisted of a convolutional neural network (CNN)-based encoder, with two auxiliary classifiers for the colon and rectum, as well as a final MES classifier that combined image features from both inputs. In the internal test, the model achieved an F1-score of 0.92, surpassing the performance of seven novice classifiers by an average margin of 0.11, and outperforming their consensus by 0.02. The area under the receiver operating characteristic curve (AUROC) was calculated to be 0.97 when considering MES 1 as positive, with an area under the precision-recall curve (AUPRC) of 0.98. In the external test using the Hyperkvasir dataset, the model achieved an F1-score of 0.89, AUROC of 0.86, and AUPRC of 0.97. The results demonstrate that the proposed CNN-based model, which integrates image features from both the colon and rectum, exhibits superior performance in accurately discriminating between MES 0 and MES 1 in patients with UC.

Incremental Detection Rate of Dysplasia and Sessile Serrated Polyps/Adenomas Using Narrow-Band Imaging and Dye Spray Chromoendoscopy in Addition to High-Definition Endoscopy in Patients with Long-Standing Extensive Ulcerative Colitis: Segmental Tandem Endoscopic Study.

High-definition (HD) endoscopy is recommended in surveillance colonoscopy for detecting dysplasia in patients with ulcerative colitis (UC). Dye-spray chromoendoscopy (DCE) and narrow-band imaging (NBI) are often used as adjunctive techniques of white-light endoscopy (WLE) in real-world practice. However, the incremental detection ability of DCE and NBI added to HD-WLE for dysplasia and serrated lesions has not yet been evaluated using tandem endoscopy in patients with long-standing extensive UC. We enrolled patients with extensive UC for >8 years who were in clinical remission (partial Mayo score < 2) at the Samsung Medical Center in Seoul, Republic of Korea. HD-WLE was performed first. Subsequently, HD-NBI and HD-DCE with indigo carmine were performed using the segmental tandem colonoscopy technique. A total of 40 patients were eligible, and data obtained from 33 patients were analyzed. The incremental detection rates (IDRs) for dysplasia and serrated lesions were calculated. HD-WLE detected three dysplasia and five sessile serrated adenomas/polyps (SSAs/Ps). HD-NBI and HD-DCE did not detect additional dysplasia (IDR = 0%; 95% confidence interval (CI): 0-56.2%). HD-NBI identified one missed SSA/P (IDR = 7.7%; 95% CI: 1.4-33.3%), and HD-DCE detected seven missed SSAs/Ps (IDR = 53.9%; 95% CI: 29.1-76.8%). Logistic regression found that HD-DCE increased the detection of SSAs/Ps compared to HD-WLE and/or HD-NBI (odds ratio (OR) = 3.16, 95% CI: 0.83-11.92, p = 0.08). DCE in addition to HD-WLE improved the detection of SSAs/Ps, but not dysplasia, in patients with long-standing extensive UC.

Histologic Activity and Steroid Use History Are Risk Factors of Clinical Relapse in Ulcerative Colitis With Mayo Endoscopic Subscore of 0 or 1.

BACKGROUND: The treatment goal of ulcerative colitis (UC) has changed from the control of symptoms to mucosal healing, previously evaluated mainly by endoscopy. Recently, the importance of histologic activity has emerged. Therefore, this study aimed to investigate the risk of clinical relapse according to histologic activity in UC with a Mayo endoscopic subsccore (MES) of 0 or 1. METHODS: In a retrospective cohort after our center's biopsy guideline for UC was instituted, 492 UC patients with an MES of 0 or 1 were enrolled and analyzed. The primary outcome was the development of a clinical relapse including changes in medication, hospitalization, colectomy, and the development of colorectal cancer during the follow-up period. RESULTS: During the median 549 days of follow-up, 92 (18.7%) patients had a clinical relapse. All the patients changed their medication, including 4 hospitalized patients. Histologic activity defined by a Geboes score of ≧3.1 (hazard ratio [HR], 1.732; P = .035) and steroid use history (HR, 1.762; P = .008) were independent factors associated with clinical relapse. When stratified, the 1- and 2-year incidence rates of clinical relapse were 4.1% and 10.6%, respectively, for patients with histologic improvement and no steroid use history, whereas the rates were 23.9% and 39.4% for patients with histologic activity and steroid use history. CONCLUSIONS: In UC with an MES of 0 or 1, histologic activity and steroid use history can be used to stratify the risk of clinical relapse.

Histologic activity defined by Geboes score of ≥3.1 and steroid use history are independent risk factors associated with clinical relapse in UC patients with Mayo endoscopic subscore of 0 or 1.

Risk of prostate cancer in patients with inflammatory bowel disease: a nationwide cohort study in South Korea.

Background: Several studies have suggested an association between inflammatory bowel disease (IBD) and the risk of prostate cancer development. However, these findings are inconsistent, and studies based on Asian populations are limited. Objectives: We compared the risk of prostate cancer according to IBD status using the Korean National Health Insurance Service database. Design: A population-based retrospective cohort of age-matched 59,044 non-IBD patients and 14,761 IBD patients between January 2009 and December 2011 was analyzed up to December 2017. Methods: The risk of prostate cancer was compared between patients with IBD and controls using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. Results: During a median follow-up of 6 years, the incidence rate of prostate cancer was 264 per 100,000 person-years in non-IBD patients and 242 per 100,000 person-years in patients with IBD. IBD status was not associated with the risk of prostate cancer compared to non-IBD [adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI): 0.80-1.08, p = 0.32). The cumulative incidence of prostate cancer did not differ by IBD status (non-IBD patients versus IBD patients: log-rank p = 0.27; non-IBD patients versus ulcerative colitis versus Crohn's disease: log-rank p = 0.42). In multivariate analysis, age was an independent risk factor for the development of prostate cancer (HR 1.03, 95% CI: 1.02-1.03, p < 0.001). Conclusion: In our population-based study, IBD status was not associated with the risk of prostate cancer.

Necessity of multiplex ligation probe amplification in genetic tests: Germline variant analysis of the APC gene in familial adenomatous polyposis patients.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary cancer syndrome characterized by hundreds to thousands of colorectal adenomatous polyps. Without treatment, progression to colorectal cancer is inevitable. Most pathogenic mutations in the APC gene were nonsense or frameshift mutations; however, some previous studies reported large deletions or duplications. METHOD: We reviewed the results of APC gene analyses from January 2010 to December 2020. We analyzed the entire coding sequence of the APC gene by Sanger sequencing to detect genetic abnormalities. Moreover, multiplex ligation-dependent probe amplification (MLPA) testing was performed starting in September 2017, and a multigene panel study that includes the APC gene was begun in July 2019. RESULTS: In the 266 collected cases, pathogenic variants/likely pathogenic variants (PV/LPVs) in the APC gene were detected in 73 patients, and variants of uncertain significance were found in 13 patients. Among those variants, 14 variants were novel. We performed MLPA for 29 patients, and 7 of them (24.1%) were positive for a large duplication/deletion. Among the 73 cases in the multigene panel study, 17 cases (23.3%) of APC gene variation were detected. CONCLUSION: We retrospectively analyzed the APC gene in Korean patients suspected to have FAP. Variants truncated by nonsense and frame shift mutations were common PV/LPVs. However, the detection rate in the MLPA study was higher than in previous studies of Caucasian populations. We suggest that MLPA should be performed for patients likely to have FAP but in whom no variant is detected by sequencing methods.

Video Capsule Endoscopy Optimal Timing in Overt Obscure Gastrointestinal Bleeding.

Video capsule endoscopy (VCE) has become the noninvasive diagnostic standard in the investigation of overt obscure gastrointestinal bleeding (OGIB), with a high positive and negative predictive value. However, the diagnostic yield of the VCE is thought to depend on when it was performed. We evaluate the optimal timing performing VCE relative to overt OGIB to improve the diagnostic yield. A total 271 patients had admitted and underwent VCE for overt OGIB between 2007 and 2016 in Samsung Medical Center, Seoul, Korea. To evaluate the diagnostic yield of VCE for overt OGIB with respect to timing of the intervention, diagnostic yield was analyzed according to the times after latest bleeding. The finding of VCE was classified into P0 or P1 (no potential for bleeding or uncertain hemorrhagic potential) and P2 (high potential for bleeding, such as active bleeding, typical angiodysplasia, large ulcerations or tumors). The P2 lesion was found in 106 patients and diagnostic yield of was 39.1% for overt OGIB. Diagnostic yield of VCE to detect P2 lesion was higher when it is performed closer to the time of latest bleeding (timing of VCE between the VCE and latest bleeding: <24 h, 43/63 (68.3%); 1 days, 16/43 (34.9%); 2 days, 18/52 (34.6%); 3 days, 13/43 (30.2%); 4 days, 7/28 (25.0%); 5-7 days, 6/24 (25.0%), and ≥8 days, 4/18 (22.2%); ptrend < 0.001). The interval between the VCE and latest bleeding were categorized into <24 h (n = 63), 1-2 days (n = 95), 3-7 days (n = 95) and ≥8 days (n = 18). Multivariable analyses showed the odds ratio for P2 lesion detection was 4.99 (95% confidence interval, 1.47-16.89) in <24 h group, compared with ≥8 days group (p < 0.010). The overall re-bleeding rate for those with P2 lesion was higher than for those with P0 or P1 lesion at the end of mean follow up of 2.5 years. The proportion of patients who underwent therapeutic intervention including surgery, endoscopic intervention and embolization was higher when VCE is performed closer to the time of latest bleeding (p = 0.010). Early deployment of VCE within 24 h of the latest GI bleeding results in a higher diagnostic yield for patients with overt OGIB and consequently resulted in a higher therapeutic intervention rate.

TNFα Induces LGR5+ Stem Cell Dysfunction In Patients With Crohn's Disease.

BACKGROUND & AIMS: Tumor necrosis factor alpha (TNFα) is considered a major tissue damage-promoting effector in Crohn's disease (CD) pathogenesis. Patient-derived intestinal organoid (enteroid) recapitulates the disease-specific characteristics of the intestinal epithelium. This study aimed to evaluate the intestinal epithelial responses to TNFα in enteroids derived from healthy controls and compare them with those of CD patient-derived enteroids. METHODS: Human enteroids derived from patients with CD and controls were treated with TNFα (30 ng/mL), and cell viability and gene expression patterns were evaluated. RESULTS: TNFα induced MLKL-mediated necroptotic cell death, which was more pronounced in CD patient-derived enteroids than in control enteroids. Immunohistochemistry and RNA sequencing revealed that treatment with TNFα caused expansion of the intestinal stem cell (ISC) populations. However, expanded ISC subpopulations differed in control and CD patient-derived enteroids, with LGR5+ active ISCs in control enteroids and reserve ISCs, such as BMI1+ cells, in CD patient-derived enteroids. In single-cell RNA sequencing, LGR5+ ISC-enriched cell cluster showed strong expression of TNFRSF1B (TNFR2) and cyclooxygenase-prostaglandin E2 (PGE2) activation. In TNFα-treated CD patient-derived enteroids, exogenous PGE2 (10 nmol/L) induced the expansion of the LGR5+ ISC population and improved organoid-forming efficiency, viability, and wound healing. CONCLUSIONS: TNFα increases necroptosis of differentiated cells and induces the expansion of LGR5+ ISCs. In CD patient-derived enteroids, TNFα causes LGR5+ stem cell dysfunction (expansion failure), and exogenous PGE2 treatment restored the functions of LGR5+ stem cells. Therefore, PGE2 can be used to promote mucosal healing in patients with CD.

Specificity of clinical decision support tools for vedolizumab and ustekinumab in biologically naïve patients with Crohn's disease.

BACKGROUND AND AIMS: Clinical decision support tools (CDST) were developed to predict drug response to various biological treatments for Crohn's disease (CD). This study investigated whether CDSTs for vedolizumab (V-CDST) and ustekinumab (U-CDST) can be used as prognostic or drug-specific markers to predict response. METHODS: A hypothetical scenario involving 872 patients with CD who were exposed to the first biological therapy at Samsung Medical Center between 1995 and 2020 is presented. V-CDST & U-CDST were calculated based on clinical and laboratory data immediately before the first biologic was initiated. The Cumulative Link Mixed Model (CLMM) test, weighted Kappa and plot, and Spearman's correlation was used to determine the degree of agreement and difference between the two tools. RESULTS: 25% of all patients diagnosed with biologically naïve CD were categorized into different probability groups using V-CDST and U-CDST. The difference between the two tools was significantly based on a two-sample paired ordinal test with Cumulative Link Mixed Model (CLMM) (p-value < .001). Concordance between the two tools with a total of 654 subjects (75% of all patients) showed a similar probability (weighted Kappa: 0.47, 95% CI: 0.41-0.52). CONCLUSIONS: V-CDST and U-CDST are useful in selecting vedolizumab or ustekinumab in 25% of biologically naïve CD patients in our hypothetical scenario.

Real-time autOmatically updated data warehOuse in healThcare (ROOT): an innovative and automated data collection system.

BACKGROUND: The American Society for Clinical Oncology recently launched the minimal common oncology data elements project to facilitate cancer data interoperability. However, clinical data are often unrecorded in an organized way, and converting them into a structured format can be time-consuming. Clinical Data Warehouse (CDW) is a database that consolidates data from different clinical sources. However, the clinical data extracted from this database include not only structured data but also natural language generated during clinical practice. Therefore, applying these data to a clinical study is challenging because they are unstructured, and unformatted to allow essential content to be found. This study determined how best to organize a huge amount of clinical data to evaluate the upper aerodigestive tract cancers' clinical features and outcomes, including cancer of the head and neck, esophagus, lung, thymus, and mesothelioma. METHODS: The Real-time autOmatically updated data warehOuse in healThcare (ROOT) uses six main regions to describe the journey of cancer patients. This study, developed an algorithm optimized for each disease category using natural language processing of unstructured data and data capture of structured data. Data from patients diagnosed at the Samsung Medical Center from 2008-2020 were used. RESULTS: Comprehensive clinical data for 67,617 patients across six tumor types: 28,954 with non-small-cell lung cancer, 2,540 with small-cell lung cancer, 30,035 with head and neck cancer, 4,950 with esophageal cancer, 966 with thymic cancer, and 172 with mesothelioma were collected. Additionally, the results of a longitudinal molecular study, including epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) tests, and next-generation sequencing (NGS), were included. Scattered information was integrated and automatically built up to match the cohort, allowing users to capture the most updated test results and treatment outcomes. CONCLUSIONS: This landmark study documented the successful construction of a real-time updating system for medical big data, based on the CDW program.

Epithelial Regeneration Ability of Crohn's Disease Assessed Using Patient-Derived Intestinal Organoids.

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn's disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.

Risk of venous thromboembolism in Asian patients with inflammatory bowel disease: a nationwide cohort study.

Routine prophylaxis for venous thromboembolism (VTE) in Asian IBD patients has been controversial. We aimed to estimate the risk of VTE of Asian patients at different phases of IBD by incorporating patient-specific risk factors. In this cohort study, we analyzed the National Health Insurance claims data between 2012 and 2016 for the entire Korean population. We calculated incidence rates and hazard ratios for VTE. The overall VTE risk was higher in patients with IBD [adjusted hazard ratio (aHR), 2.06; 95% confidence interval (CI), 1.66-2.55], than in controls. When we compare the risk of VTE by different disease phases, the risk of VTE was the highest during post-operation period after IBD-related bowel surgery (aHR, 39.7; 95% CI 9.87-159.3), followed by during hospitalized periods with flare (aHR, 27.2; 95% CI 14.9-49.65) and during hospitalized periods with non-flare (aHR, 16.23; 95% CI 10.71-24.58). The incidence rate (per 1000 person-years) was 15.26 during hospitalized periods with a flare and 9.83 during hospitalized periods with non-flare. According to age groups, the incidence rate (per 1000 person-years) during hospitalized periods with flare was 14.53 in young patients (20-39 years) and 34.58 in older patients (60-80 years). During hospitalized periods with non-flare, the incidence rate was 3.55 in young patients and 23.61 in older patients. The prophylaxis of VTE for Asian patients with IBD should be recommended in older patients admitted to hospital and be considered in young patients who are hospitalized with a flare.

Depletion of Intestinal Stem Cell Niche Factors Contributes to the Alteration of Epithelial Differentiation in SAMP1/YitFcsJ Mice With Crohn Disease-Like Ileitis.

BACKGROUND: SAMP1/YitFcsJ (SAMP1) mice spontaneously develop terminal ileitis resembling human Crohn disease. SAMP1 mice have exhibited alteration of epithelial cell lineage distribution and an overall proliferation of the crypt cell population; however, it has not been evaluated whether epithelial differentiation is impaired because of dysfunction of intestinal stem cells (ISCs) or their niche factors. METHODS: Using the intestine of SAMP1 mice aged 10 to 14 weeks, morphometric alterations in the crypt-villus architecture, ISCs, crypt cells, and differentiated cells; organoid formation capacity of intestinal crypts; and niche signaling pathways were analyzed and compared with those of age-matched control AKR/J (AKR) mice. RESULTS: The ileum of SAMP1 mice showed increased depth of intestinal crypts and decreased surface area of the villi compared with those in the ileum of AKR mice. The number of ISCs in the ileal crypts did not differ between SAMP1 and AKR mice; however, the number of Paneth cells decreased and the number of transient amplifying cells increased. The organoid formation rate of the ileal crypts of SAMP1 mice decreased significantly compared with that of AKR mice. The performance of RNA sequencing for intestinal crypts found that the expression of ISC niche factors, such as Wnt3, Dll1, and Dll4, was decreased significantly in the ileal crypts of SAMP1 mice compared with those of AKR mice. Among the ISC niche signals, the Notch signaling-related genes tended to be downregulated. In particular, immunocytochemistry revealed that the expression of Paneth cell-expressing Notch ligand Dll4 was significantly decreased in the intestinal tissue and organoids of SAMP1 mice compared with those of AKR mice. CONCLUSIONS: Depletion of niche factors for ISCs contributes to the alteration of epithelial differentiation in SAMP1 mice.