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Summary Background Aims Methods Results Conclusions The impact of continuing or stopping 5‐aminosalicylates (5‐ASA) after commencing anti‐tumour necrosis factor (anti‐TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear.To compare the outcomes of patients with IBD who stopped or continued 5‐ASA after starting anti‐TNF therapy.We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5‐ASA within 90 days of anti‐TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD‐related hospitalisation, or intestinal surgery.Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5‐ASA within 90 days of starting anti‐TNF therapy. During a median 4.3‐year follow‐up, discontinuation of 5‐ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93–1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5‐ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups.In this nationwide population‐based study, discontinuing 5‐ASA after starting anti‐TNF therapy was not associated with an increased risk of adverse events in patients with IBD. [ABSTRACT FROM AUTHOR]

Fecal calprotectin (FC) is commonly used to assess Crohn's disease (CD) activity. However, standardized cut-off values accounting for bowel resection history and disease location are lacking. In this study, we analyzed data from patients with CD who underwent magnetic resonance enterography, ileocolonoscopy, and FC measurements from January 2017 to December 2018. In 267 cases from 254 patients, the FC levels in the 'operated' patients were higher when the disease was active compared with those who were in the remission group (178 vs. 54.7 μg/g; p < 0.001), and similar findings were obtained for the 'non-operated' patients (449.5 vs. 40.95 μg/g; p < 0.001). The FC levels differed significantly according to the location of inflammation, with lower levels in the small bowel compared to those in the colon. The FC cut-off levels of 70.8 μg/g and 142.0 μg/g were considered optimal for predicting active disease for operated and non-operated patients, respectively. The corresponding FC cut-off levels of 70.8 μg/g and 65.0 μg/g were observed for patients with disease only in the small bowel. In conclusion, different FC cut-off values would be applicable to patients with CD based on their bowel resection history and disease location. Tight control with a lower FC target may benefit those with a history of bowel resection or small-bowel-only disease. [ABSTRACT FROM AUTHOR]

Background and Aim: Low‐volume bowel preparation solutions, including 1‐L polyethylene glycol plus ascorbate (PEG‐A), have been developed to improve tolerability. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. We investigated the efficacy, safety, and tolerability of OST compared to 1‐L PEG‐A. Methods: A single‐center, prospective, controlled study was performed with randomization into the OST (group A) and 1‐L PEG‐A (group B) groups. Bowel preparation efficacy was assessed on the Boston Bowel Preparation Scale (BBPS) and Bubble Scale. Safety and tolerability were evaluated using a questionnaire and laboratory examination. Results: Final analysis was performed on 171 patients (group A: 87, group B: 84). The proportion of bowel preparation success (BBPS ≥ 2 for each colonic segment) in group A was not inferior compared to group B (95.4% vs 96.4%, P = 0.736, 1‐sided 97.5% lower confidence limit −7.0%). The adenoma detection rate was not different (59.6% vs 41.9%; P = 0.087). The bubble scale was better in group A (0.2 ± 0.9 vs 1.9 ± 1.7, P < 0.001). All adverse events were mild in both groups. Nausea was less frequent in group A (14.9% vs 38.1%, P = 0.001). Overall satisfaction was better in group A (8.1 ± 2.1 vs 6.4 ± 2.8, P < 0.001). No clinically significant laboratory abnormality developed in both groups. These findings were similarly shown in old patients ≥65 years. Conclusions: Both OST and 1‐L PEG‐A were efficacious, safe, and tolerable for bowel preparation of colonoscopy. The OST showed fewer bubbles and slightly better tolerability. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aimed to investigate the effect of stenting‐related factors, including endoscopists' expertise, on clinical outcomes after bridge‐to‐surgery (BTS) stenting for obstructive colorectal cancer (CRC). Methods: We analyzed BTS stenting‐related factors, including stenting expertise and the interval between stenting and surgery, in 233 patients (63 [13] years, 137 male) who underwent BTS stenting for obstructive CRC. We evaluated the influence of these factors on post‐BTS stenting clinical outcomes such as stent‐related complications and cancer recurrence. Results: The interval between stenting and surgery was ≤ 7 days in 79 patients (33.9%) and > 7 days in 154 patients (66.1%). BTS stenting was performed by endoscopists with ≤ 50, 51–100, and > 100 prior stenting experiences in 94, 43, and, 96 patients, respectively. The clinical success rate of BTS stenting was 93.1%. Stent‐related and postoperative complications developed in 19 (8.2%) and 20 (8.6%) patients, respectively. Cancer recurrence occurred in 76 patients (32.6%). Short BTS interval of ≤ 7 days increased the risk of postoperative complications (odds ratio [OR], 2.61 [1.03–6.75]; P = 0.043). Endoscopists' stenting experience > 100 showed greater clinical success of stenting (OR, 5.50 [1.45–28.39]; P = 0.021) and fewer stent‐related complications (OR, 0.26 [0.07–0.80]; P = 0.028) compared with stenting experience ≤ 50. BTS stenting‐related factors did not affect long‐term oncological outcomes. Conclusion: Greater expertise of endoscopists was associated with better short‐term outcomes, including high stenting success rate and low rate of stent‐related complications after BTS stenting for obstructive CRC. An interval of > 7 days between BTS stenting and surgery was required to decrease postoperative complications. [ABSTRACT FROM AUTHOR]

Background and Aims: Reduced body muscle mass is a poor prognostic factor for inflammatory bowel disease (IBD). In this study, we investigated the prevalence of sarcopenia at diagnosis and its clinical significance in Korean patients with IBD. Methods: The prevalence of sarcopenia in IBD patients between June 1989 and December 2016 was investigated using a well-characterized referral center-based cohort. Abdominopelvic computed tomography within six months from IBD diagnosis was used for the evaluation. Sarcopenia was defined as an L3 skeletal muscle index of < 49 cm2/m2 for male and < 31 cm2/m2 for female. The clinical characteristics and outcomes were evaluated with respect to sarcopenia. Results: A total of 1,027 patients (854 Crohn's disease [CD]; 173 ulcerative colitis [UC]) were evaluated. Sarcopenia was found in 56.8% of the population (CD, 57.5%; UC, 53.2%), and male were more likely to be sarcopenic (CD, 94.3%; UC, 91.6%). There were no significant differences in the cumulative risk of using steroids, immunomodulators, biologics, and bowel resections (or colectomy) with or without sarcopenia during follow-up (median: CD, 5.8 years; UC, 3.7 years). In sarcopenic patients with CD, there was a significantly higher cumulative risk of perianal surgeries than in non-sarcopenic patients with CD (Log-rank test; P = 0.001). However, the risk of perianal surgeries was not significant in multivariate analysis (Odds ratio 1.368; 95% confidence interval 0.782–2.391; P = 0.272). Conclusion: Sarcopenia at diagnosis may have no significant prognostic value for medical treatment and bowel resection, but it may be associated with perianal CD. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration. [ABSTRACT FROM AUTHOR]

The clinical usefulness of repeat colonoscopic polypectomy in patients with numerous polyps has not been sufficiently determined. We aimed to analyze the clinical outcomes of colonoscopic polypectomy with surveillance colonoscopies in patients with ≥ 10 polyps. We reviewed the medical records of 152 patients who underwent polypectomy of ≥ 10 polyps at the baseline colonoscopy. We investigated polyp number, polyp size, polypectomy method, procedure time, and adverse events of the baseline colonoscopy. We also investigated the frequency and interval of surveillance colonoscopies and their findings. The mean number of polyps detected at the baseline colonoscopy was 20.0, of which 16.0 polyps were endoscopically resected. The mean size of the largest polyp was 13.4 mm. The mean procedure time was 54.9 min. Post-polypectomy bleeding occurred in 6 (3.9%) patients, all of whom were treated conservatively. No patients developed perforation. With an increasing number of surveillance colonoscopies, the number of detected polyps and the procedure time decreased. Surveillance colonoscopies identified colorectal cancer only in three patients (2.0%), all of which were mucosal cancers that could be curatively treated by polypectomy. Colonoscopic polypectomy with repeat surveillance colonoscopies is a clinically effective, efficient, and safe management option in patients with ≥ 10 polyps. [ABSTRACT FROM AUTHOR]

Objectives: Post‐polypectomy surveillance intervals should be determined based on index colonoscopy findings. However, the risk of metachronous lesions, resulting from the coexistence of adenoma and sessile serrated lesions (SSLs), has rarely been addressed. We evaluated the impact of synchronous SSL on the risk of metachronous lesions within similar adenoma risk groups. Methods: We retrieved individuals with one or more adenomas on index colonoscopy in a single‐center retrospective cohort and stratified them into four groups depending on the presence of SSL and low‐risk/high‐risk adenoma (LRA/HRA). Participants who underwent surveillance colonoscopies at least 12 months apart were included. We compared the risks of metachronous lesions including HRA, advanced adenoma (AA), or SSL within similar adenoma risk groups according to the presence of SSL. Results: Overall 4493 individuals were included in the analysis. The risk of metachronous HRA/AA was not significantly higher in the adenoma with SSL group compared with the adenoma without SSL group, irrespective of LRA (HRA, 6/86 vs. 231/3297, P = 1.00; AA, 0/86 vs. 52/3297, P = 0.64) or HRA (HRA, 11/64 vs. 240/1046, P = 0.36; AA, 3/64 vs. 51/1046, P = 1.00). However, the risk of metachronous SSL in individuals with synchronous SSL was higher than that in those without SSL for both LRA (15/86 vs. 161/3297, P < 0.001) and HRA groups (11/64 vs. 61/1046, P = 0.002). Conclusion: The presence of synchronous SSL did not increase the risk of metachronous HRA/AA, compared with isolated adenoma, but increased the risk of metachronous SSL. [ABSTRACT FROM AUTHOR]

Background and Aim: Evidence has emerged that a pretreatment immune profile in rectal cancer is associated with response to chemoradiotherapy (CRT) and recurrence after CRT. However, few studies have evaluated the immune profile differences after CRT regarding recurrence and nonrecurrence. Methods: We included patients with advanced rectal cancer treated with CRT and surgery with recurrence within 1 year in a recurrence group. After sex and age matching with the recurrence group, patients with no recurrence for 3 years after CRT were included in a nonrecurrence group. We extracted the immune profile, including CD3 and CD8, from the surgical specimen after CRT using multispectral fluorescence immunohistochemistry and compared the two groups. Results: The immune profiles of 65 patients with rectal cancer were assessed; 30 were included in the recurrence group and 35 were included in the nonrecurrence group. CD3+ and CD8+ T lymphocyte densities were significantly higher in the nonrecurrence group than in the recurrence group (CD3+; P < 0.001, CD8+; P = 0.003) in the primary tumor. Consistent results were found in epithelial and stromal cells. Compared with the recurrence group, the distinct profiles of co‐expressed immune markers in the nonrecurrence group were revealed (CD3+CD8+, P = 0.001; CD3+CD8+PD‐L1−, P = 0.001; CD3+CD8+ FOXP3− PD‐L1−, P = 0.001). Conclusions: Vigorous CD3+ and CD8+ T cell priming post‐CRT was prominent in the nonrecurrence group compared with that of the recurrence group. This finding suggests that differences in immune profiles may have clinical significance even after CRT. [ABSTRACT FROM AUTHOR]

Background: Chronic viral hepatitis is associated with a wide range of extrahepatic diseases; however, evidence on a link between chronic viral hepatitis and colorectal neoplasia is still lacking. Aims: To analyze the association between chronic viral hepatitis and prevalence of colorectal neoplasia. Methods: A systematic review of articles published in the MEDLINE, EMBASE, and Cochrane Library between 2000 and 2020 was performed. Subgroup analyses based on the types of colorectal neoplasia and the etiology of chronic viral hepatitis were conducted. Results: Twelve eligible studies with 48,428 hepatitis B virus (HBV) patients and 46,561 hepatitis C virus (HCV) patients were included. Chronic viral hepatitis was significantly associated with an increased risk of both colorectal adenoma (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.16–2.02; I2 = 83%) and colorectal cancer (CRC) (OR, 1.32; 95% CI, 1.08–1.61; I2 = 94%). The etiology of chronic viral hepatitis was an independent factor related to heterogeneity for CRC subgroup analysis revealed an increased risk of CRC in both HBV (OR, 1.18; 95% CI, 1.09–1.27; I2 = 37%) and HCV (OR, 1.88; 95% CI, 1.78–1.97; I2 = 0%). HCV was associated with an increased risk of colorectal adenoma (OR, 1.48; 95% CI, 1.22–1.79; I2 = 0%); however, HBV was not associated with an increased risk of colorectal adenoma and had considerable heterogeneity (OR, 1.65; 95% CI, 0.88–3.09; I2 = 90%). Conclusion: Our meta-analysis showed that chronic viral hepatitis is associated with an increased risk of colorectal neoplasia. The strategy of stricter screening colonoscopy may benefit from patients with chronic viral hepatitis. [ABSTRACT FROM AUTHOR]

Background: Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment.Methods: The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn's disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group.Results: Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014-1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262-3.066, p = 0.862).Conclusions: In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy. [ABSTRACT FROM AUTHOR]

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn's disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn's disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX (p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration. [ABSTRACT FROM AUTHOR]

Background: The Rutgeerts score is used to predict postoperative recurrence in CD patients after ileocolic resection and is primarily based on endoscopic findings at the neoterminal ileum. However, the optimal assessment of anastomotic ulcers (AUs) remains subject to debate. Aims: We aimed to investigate the association between anastomotic ulcers (AUs) and endoscopic recurrence in postoperative Crohn's disease (CD) patients. Methods: This single-center retrospective study, conducted between 2000 and 2016, evaluated postoperative CD patients with endoscopic remission at the first ileocolonoscopy within 1 year after ileocolic resection and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs in predicting endoscopic recurrence. Results: Among 116 patients who were in endoscopic remission defined as the RS of i0 to i1 at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the median 30.0 months (interquartile range, 21.3–53.3) of follow-up after the first ileocolonoscopy, 56.1% (55/98) of patients showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs, defined as either an ulcer occupying ≥ 1/4 of the circumference, ≥ 3 ulcers confined to anastomotic ring, or any ulcers extending to the ileocolonic mucosa, showed endoscopic recurrence. On multivariable analysis, AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87–10.0; P < 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95–79; P < 0.001) were associated with endoscopic recurrence. Conclusions: AUs are associated with a significantly high risk of endoscopic recurrence in postoperative CD patients who are in endoscopic remission. [ABSTRACT FROM AUTHOR]

Background and Aim: Data comparing the outcomes of cyclosporin A (CsA) and infliximab (IFX) as rescue therapy for steroid‐refractory acute severe ulcerative colitis (SR‐ASUC) among Asians are scarce. Methods: In this single‐center study, we retrospectively reviewed 121 patients with SR‐ASUC according to the Truelove and Witts' criteria who received CsA or IFX as rescue therapy between 1995 and 2015. The cumulative rates of treatment failure and colectomy at 3 months were compared. Treatment failure was defined as colectomy, switch to other medications, acute flare‐up events requiring steroid treatment, or adverse events leading to drug interruption. Results: Among 121 patients with SR‐ASUC (male, 55.6%; median disease duration, 47.1 months; extensive colitis, 61.2%), 23 received CsA as rescue therapy. Baseline characteristics (e.g. age at diagnosis, sex, disease duration, disease extent at rescue therapy, and Mayo score at treatment initiation) were comparable between the two groups. During follow‐up (median, 45 months; interquartile range 29.3–61.8), 84 patients (69.4%) experienced treatment failure, and 25 patients (20.7%) underwent colectomy. The CsA group and the IFX group did not show significant differences in the cumulative rates of treatment failure (39.1% vs 34.7%, P = 0.714) and colectomy (26.1% vs 13.3%, P = 0.198) at 3 months. Previous use of azathioprine (odds ratio [OR] = 2.309, 95% confidence interval [CI] = 1.076–4.951, P = 0.032) was associated with treatment failure at 3 months. Mayo score > 10 at the time of rescue therapy was significantly associated with colectomy at 3 months (OR = 8.444, 95% CI = 2.592–27.506, P < 0.001). Conclusion: Among Korean patients with SR‐ASUC, the rates of treatment failure and colectomy at 3 months were not significantly different between the CSA and the IFX treatment groups. [ABSTRACT FROM AUTHOR]

Background and Aim: Acute severe lower gastrointestinal bleeding (LGIB) in patients with Crohn's disease (CD) is uncommon; however, it is a potentially life‐threatening complication, and its recurrence is common. We thus aimed to identify the predictors for rebleeding in CD patients with acute severe LGIB and particularly focused on whether anti‐tumor necrosis factor (TNF) therapy lowers the risk of rebleeding compared with conventional medical therapy (CMT) or surgery. Methods: The risk of rebleeding was analyzed in 131 CD patients with acute severe LGIB. Patients were classified into the CMT group (n = 99), anti‐TNF therapy group (n = 22), and surgery group (n = 10). No patients in the surgery group received anti‐TNF therapy. Results: During the median follow‐up of 98 months after the first episode of acute severe LGIB, rebleeding occurred in 50.5%, 18.2%, and 30.0% of the CMT group, anti‐TNF therapy group, and surgery group, respectively (P = 0.015). The cumulative risks of rebleeding at 1 and 10 years were 20.0% and 64.7% in the CMT group, 13.6% and 18.4% in the anti‐TNF therapy group, and 0% and 40.7% in the surgery group, respectively (P = 0.020). Multivariable Cox regression analysis showed that anti‐TNF therapy was associated with a lower risk of rebleeding compared with CMT (hazard ratio, 0.303; 95% confidence interval, 0.108–0.849; P = 0.023). Conclusions: In CD patients with acute severe LGIB, anti‐TNF therapy may reduce the risk of rebleeding compared with CMT. Although surgery is considered effective in preventing early rebleeding, concomitant anti‐TNF therapy may be helpful in further lowering the long‐term risk of rebleeding. [ABSTRACT FROM AUTHOR]

For the sensitive diagnosis of colorectal cancer lesions, advanced molecular imaging techniques using cancer-specific targets have emerged. However, issues regarding the clearance of unbound probes and immunogenicity remain unresolved. To overcome these limitations, we developed a small-sized scFv antibody fragment conjugated with FITC for the real-time detection of colorectal cancer by in vivo molecular endoscopy imaging. A small-sized scFv fragment can target colon cancer secreted protein-2 (CCSP-2), highly expressed in colorectal adenocarcinoma tissues; moreover, its full-length IgG probe has been used for molecular imaging previously. To assess the efficacy of anti-CCSP-2 scFv-FITC, surgical specimens were obtained from 21 patients with colorectal cancer for ex vivo molecular fluorescence analysis, histology, and immunohistochemistry. Orthotopic mice were administered with anti-CCSP-2 scFv-FITC topically and intravenously, and distinct tumor lesions were observed by real-time fluorescence colonoscopy. The fluorescence imaging of human colon cancer specimens allowed the differentiation of malignant tissues from non-malignant tissues (p < 0.05), and the CCSP-2 expression level was found to be correlated with the fluorescence intensity. Here, we demonstrated the feasibility and safety of anti-CCSP-2 scFv-FITC for molecular imaging as well as its potential in real-time fluorescence colonoscopy for the differential diagnosis of tumor lesions. [ABSTRACT FROM AUTHOR]

Small rectal neuroendocrine tumors (NETs) can be treated using cap-assisted endoscopic mucosal resection (EMR-C), which requires additional effort to apply a dedicated cap and snare. We aimed to evaluate the feasibility of a simpler modified endoscopic mucosal resection (EMR) technique, so-called anchored snare-tip EMR (ASEMR), for the treatment of small rectal NETs, comparing it with EMR-C. We retrospectively evaluated 45 ASEMR and 41 EMR-C procedures attempted on small suspected or established rectal NETs between July 2015 and May 2020. The mean (SD) lesion size was 5.4 (2.2) mm and 5.2 (1.7) mm in the ASEMR and EMR-C groups, respectively (p = 0.558). The en bloc resection rates of suspected or established rectal NETs were 95.6% (43/45) and 100%, respectively (p = 0.271). The rates of histologic complete resection of rectal NETs were 94.1% (32/34) and 88.2% (30/34), respectively (p = 0.673). The mean procedure time was significantly shorter in the ASEMR group than in the EMR-C group (3.12 [1.97] vs. 4.13 [1.59] min, p = 0.024). Delayed bleeding occurred in 6.7% (3/45) and 2.4% (1/41) of patients, respectively (p = 0.618). In conclusion, ASEMR was less time-consuming than EMR-C, and showed similar efficacy and safety profiles. ASEMR is a feasible treatment option for small rectal NETs. [ABSTRACT FROM AUTHOR]

Background and Aim: The clinical impact of perianal Crohn's disease (CD) (pCD), a well‐known poor prognostic factor of CD, has not been fully evaluated in Asian patients. We investigated the outcomes of CD in Korean patients according to the presence of pCD at CD diagnosis. Methods: Using 2010–2014 data from the national health insurance claims database, we evaluated the disease course of CD according to the presence of pCD at CD diagnosis. The results were verified in a hospital‐based cohort of 2923 patients. Results: The cumulative risk of intestinal resection was lower in patients with pCD at diagnosis than in those without, in the population‐based cohort (9.1% vs 14.7% at 5 years after diagnosis, P < 0.001), but it was similar between the two groups in the hospital‐based cohort (36.8% vs 36.8% at 10 years after diagnosis, P = 0.950). Moreover, the cumulative risk of behavioral progression was not significantly different between the two groups in the hospital‐based cohort (43.4% vs 41.6% at 10 years after diagnosis, P = 0.366). On multivariable analysis, pCD at CD diagnosis was not a predictor of intestinal resection, behavioral progression, CD‐related hospital admission, or diverting surgery; however, it was an independent predictor of proctectomy (hazard ratio [HR] 3.210, P < 0.001) and anorectal cancer (HR 3.104, P = 0.047). Conclusions: Although the presence of pCD increased the risk of proctectomy and anorectal cancer in Asian patients, the clinical impact of pCD on the overall outcomes of patients with CD may be less significant in Asian patients compared with Western patients. [ABSTRACT FROM AUTHOR]

We aimed to investigate the endoscopic features and clinical course of CMV gastroenterocolitis in immunocompetent patients. We reviewed the medical records and endoscopic images of 86 immunocompetent patients with CMV gastroenterocolitis. Immunocompetent patients were defined as those without congenital or acquired immunodeficiency syndrome, use of anti-cancer chemotherapeutic and immunosuppressive agents, and inflammatory bowel diseases. The mean age was 65.5 ± 11.8 years and 53 (61.6%) were male. Sixty-eight (79.1%) patients had comorbidities. Upper gastrointestinal-dominant, small bowel-dominant, and colon-dominant types were observed in 19, 7, and 60 patients, respectively. Endoscopic features could be classified into discrete ulcerative type with/without exudate and diffuse erythematous type with/without exudate. Antiviral treatment with ganciclovir was initiated in 51 patients (59.3%), 40 of whom improved and 1 improved after changing ganciclovir to foscarnet. Thirty-three patients (38.4%) improved without antiviral treatment. Surgery was necessary in two patients because of colon perforation before antiviral treatment. Another two patients underwent surgery because of sigmoid stricture and cecal perforation during antiviral treatment. Endoscopic type was not associated with clinical outcomes, such as surgery and death. CMV gastroenterocolitis in immunocompetent patients mostly occur in older patients with comorbidities, and the endoscopic features vary with no association with clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown vitamin D status to be associated with disease activity in patients with inflammatory bowel disease (IBD), but its influence on the clinical course of IBD has not been established. Aims: We aimed to analyze whether the serum 25-hydroxyvitamin D3 [25(OH)D] status is associated with clinical characteristics and affects the risk of surgery in patients with IBD. Methods: From the IBD registry of the Asan Medical Center, we identified all patients who had at least one 25(OH)D measurement; we then analyzed the association between clinical factors and 25(OH)D status. 25(OH)D was considered borderline deficient, deficient, and severely deficient at levels of < 30, < 20, and < 10 ng/mL, respectively. Results: We included 711 Crohn's disease (CD) and 764 ulcerative colitis (UC) patients who had not undergone surgery before 25(OH)D was measured. Both in CD and in UC patients, reduced 25(OH)D was associated with higher disease activity scores and CRP levels (p < 0.001). Severe 25(OH)D deficiency was associated with ileocolonic disease and complicated behavior in CD (p < 0.05) and was relevant to the disease extent in UC (p < 0.001). Additionally, severe 25(OH)D deficiency was associated with CMV colitis in patients with UC (p < 0.001). In multivariable analysis, severe deficiency of 25(OH)D was an independent risk factor for surgery in both CD (HR 1.93, 95% confidence interval [CI] 1.38–2.70) and UC (HR 2.77, 95% CI 1.14–6.74). Conclusion: Severe 25(OH)D deficiency may be a marker of a more aggressive clinical course of IBD. [ABSTRACT FROM AUTHOR]

The usage of direct oral anticoagulants (DOACs) to prevent and treat thromboembolic events is gradually increasing. We aimed to evaluate the outcomes of patients taking DOACs after polypectomy. We retrospectively reviewed 131 patients taking DOACs and 270 taking clopidogrel who underwent polypectomy between November 2010 and December 2017. The risk of delayed postpolypectomy bleeding (PPB) was evaluated and compared. A total of 989 polyps were removed (320 polyps in the DOAC and 669 polyps in the clopidogrel group). DOACs and clopidogrel were discontinued for 2.8 ± 1.7 days and 5.8 ± 2.5 days before polypectomy, respectively. DOACs and clopidogrel were restarted on 1.6 ± 2.9 days and 1.7 ± 1.1 days after polypectomy, respectively. According to per polyp analysis, delayed PPB rate was 1.6% in both groups (p = 0.924). Logistic regression analysis was performed after propensity score matching and revealed that DOACs did not increase the delayed PPB risk compared to clopidogrel (OR 0.929, 95% CI 0.436–1.975, p = 0.847). With the majority following the antithrombotic discontinuation guidelines, the incidence of delayed PPB was 3.1% in the patients taking DOACs. The delayed PPB risk was not greater in those taking DOACs than in those taking clopidogrel. [ABSTRACT FROM AUTHOR]

Background: Many patients with ulcerative colitis (UC) in clinical remission frequently complain of bowel symptoms such as increased stool frequency (SF) and rectal bleeding (RB). However, studies on these patient-reported outcomes in patients with inactive UC are limited, especially in Korea. Therefore, we investigated the prevalence and risk factors of bowel symptoms in Korean patients with inactive UC.Methods: We investigated the prevalence of bowel symptoms in patients with endoscopically quiescent UC between June 1989 and December 2016 using a well-characterized referral center-based cohort. The Mayo clinic score (MCS) was used to evaluate bowel symptoms at the most recent visit near the date of endoscopy. Clinical characteristics of the patients were compared based on the presence or absence of bowel symptoms.Results: Overall, 741 patients with endoscopically quiescent UC were identified, of whom 222 (30%) and 48 (6.5%) had an SF and RB subscore of ≥ 1, respectively. Patients with bowel symptoms (SF + RB ≥ 1; n = 244 [32.9%]) had higher rates of left-sided colitis (E2) or extensive colitis (E3) than patients without bowel symptoms (SF + RB = 0; n = 497 [67.1%]; P = 0.002). Multivariate analysis revealed that female sex (odds ratio [OR]: 1.568; 95% confidence interval [CI]: 1.023-2.402; P = 0.039) and E2 or E3 (OR 1.411; 95% CI 1.020-1.951; P = 0.038) were the significant risk factors for increased SF.Conclusions: This study revealed that one-third of patients with endoscopically quiescent UC reported increased SF. Female sex and disease extent may be associated with bowel symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn's disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn's disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX (p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration. [ABSTRACT FROM AUTHOR]

Background: Esophageal bolus transit can be assessed using esophagogram or high‐resolution impedance manometry (HRIM). The three‐dimensional volume of inverted impedance (VII) has been developed to quantify the residual bolus between each swallow through spatiotemporal analysis. However, this novel metric has not been validated against simultaneous esophagogram. Methods: A total of nine healthy volunteers (Seven males, aged 19‐45 years) were prospectively evaluated with HRIM and barium esophagogram. In addition, 21 symptomatic patients (12 males, aged 20‐85 years) without major motility disorder were also included. The VII was estimated from HRIM data using MATLAB program and was compared with residual bolus volume in the esophagus estimated from simultaneous esophagogram. Key results: A total of 80 swallows (24 in controls and 56 in patients) were analyzed. Results from the VII method were concordant with the bolus transit pattern estimated from the esophagogram in 91.3% (73/80) of swallows. The correlation between quantitative data from VII and the volume of residual bolus estimated from esophagogram was strong in both groups with a Pearson's correlation coefficient of 0.805 for healthy volunteers and 0.730 for symptomatic patients. The intraclass correlation coefficient of VII between the three swallows within a subject was 0.901 in healthy subjects and 0.705 in patients, indicating a modest reliability of this method. Conclusions and inferences: The newly developed VII method is a reliable method in assessing residual bolus volume in the esophagus based on comparison with bolus volume estimated from simultaneous esophagogram. [ABSTRACT FROM AUTHOR]

Purpose: A modified endoscopic mucosal resection (EMR) technique, Tip-in EMR, was recently introduced to enhance the complete resection of colorectal neoplasia (CRN). We aimed to evaluate the feasibility of Tip-in EMR for flat CRNs. Methods: From January to September 2018, conventional or Tip-in EMR was consecutively performed for 112 flat CRNs ≥ 10 mm in diameter. Tip-in EMR was performed when en bloc snaring was impossible with conventional EMR or when a lesion was inadequately lifted owing to a previous forceps biopsy. We retrospectively collected the clinical, procedural, and histologic data of the conventional and Tip-in EMR groups and compared the en bloc resection rate, complete resection rate, and complications between the two groups. Results: Among 112 flat CRNs of 80 patients, conventional EMR and Tip-in EMR were performed for 74 and 38 lesions, respectively. The median lesion size was 12 (10–27) mm. Tip-in EMR was superior to conventional EMR in terms of en bloc resection (94.7% vs. 77.0%, p = 0.018) and histologic complete resection (76.3% vs. 54.1%, p = 0.022). There was no difference in postprocedural bleeding between the two groups; however, overall adverse events, including bleeding and postpolypectomy electrocoagulation syndrome, were more frequent in the Tip-in EMR group. Conclusions: Tip-in EMR is a feasible technique for flat colorectal lesions ≥ 10 mm and is superior to conventional EMR with respect to en bloc and complete resection rates. The safety profiles of Tip-in EMR and conventional EMR should be compared via large-scale prospective studies. [ABSTRACT FROM AUTHOR]

Background and Aims: The phenotypic concordance among familial cases of inflammatory bowel disease (IBD) has been rarely reported. Thus, the present study aimed to evaluate the concordance regarding disease type and phenotypic features in a large cohort of Korean patients with IBD. Methods: A total of 6647 patients with IBD who visited the Asan Medical Center between June 1989 and September 2016 were enrolled in the study. When at least two familial cases existed in our cohort, they were included in the concordance analysis (κ index). The concordance between younger and older members for IBD type [Crohn's disease (CD) and ulcerative colitis (UC)] and phenotypic characteristics such as disease extent and location, disease behavior, the use of medication, and need for surgery were evaluated. Results: A positive family history of IBD was noted in 216 patients with CD (7.0%) and in 238 patients with UC (6.7%). Of all patients, 167 consanguineous pairs in 146 families were identified. The crude concordance rate for IBD type was 82.6% with a κ index of 0.656 [95% confidence interval (CI): 0.545–0.768, good concordance]. There was mild concordance for disease location in CD (κ = 0.256; 95% CI: 0.007–0.505) and for the use of antitumor necrosis factor agents in UC (κ = 0.354; 95% CI: −0.049–0.757). The concordance for IBD type and several phenotypes in first‐degree relative pairs was better than that in the entire pairs. Conclusions: Disease type and phenotypic characteristics of patients with familial IBD may be anticipated. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the costs of colorectal endoscopic submucosal dissection (ESD) and endoscopic piecemeal mucosal resection (EPMR).Aims: Here, we aimed to investigate the cost-effectiveness of these approaches by analyzing clinical outcomes and costs.Methods: Data from patients undergoing colorectal ESD and EPMR were retrospectively reviewed. Clinical outcomes (procedure time, complete resection, and recurrence) were compared, and total direct costs (procedural and follow-up) were assessed.Results: Data from 429 ESD and 115 EPMR patients were included in the analysis. The complete resection rate was significantly higher (83.9% vs. 32.2%, p < 0.001), recurrence rate was lower (0.5% vs. 7.1%, p < 0.001), procedure time was longer (55.4 ± 47.0 vs. 25.6 ± 32.7 min, p < 0.001), and total direct procedural costs at the initial resection were higher (1480.0 ± 728.0 vs. 729.8 ± 299.7 USD, p < 0.001) in the ESD group than in the EPMR group. The total number of surveillance endoscopies was higher in the EPMR group (1.7 ± 1.5 vs. 1.3 ± 1.1, p = 0.003). The cumulative total costs of ESD and EPMR were comparable at 3 and 2 years' follow-up in the adenoma and mucosal/superficial submucosal cancer subgroups, respectively.Conclusions: Colorectal ESD was associated with higher complete resection and lower recurrence rates. EPMR showed shorter procedure times and similar cumulative total direct costs. ESD or EPMR should be chosen based on both clinical outcomes and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Little is known about the natural history of perianal fistulas in Asian populations with Crohn's disease (CD).Aims: We investigated the incidence and outcomes of perianal CD (pCD) in Korean CD patients.Methods: A nationwide population-based cohort of 6265 CD patients diagnosed in 2010-2014 was analyzed to investigate the incidence and outcomes of pCD. The results were validated in a hospital-based cohort of 2923 CD patients diagnosed in 1981-2015. Factors associated with pCD development were analyzed. The incidence and outcomes of pCD were compared between the prebiologic and biologic eras.Results: pCD occurred in 39.2% of the population-based cohort and 56.1% of the hospital-based cohort during the median follow-up of 4.2 and 8.5 years, respectively. The cumulative incidence of pCD was 40.0% at 5 years after CD diagnosis in the population-based cohort and 62.5% at 20 years in the hospital-based cohort. In multivariate analysis, pCD development was positively associated with male sex, younger age and colonic involvement at diagnosis, early diagnosis, and CD diagnosis in the prebiologic era. The cumulative probability of proctectomy at 10, 20, and 30 years after pCD diagnosis was 2.9%, 12.2%, and 16.2%, respectively. The cumulative incidence of pCD occurring after CD diagnosis and the cumulative probability of proctectomy were significantly lower in the biologic era than in the prebiologic era (p < 0.001 and p = 0.03, respectively).Conclusions: Compared with Western patients with CD, Korean patients show a high incidence of pCD but have a low probability of proctectomy, suggesting the favorable course of pCD. [ABSTRACT FROM AUTHOR]

Background and Aim: Little is known whether routine prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is needed in patients with inflammatory bowel disease (IBD) on immunosuppression, especially in Asian populations. We, therefore, sought to investigate the incidence and risk factors of PJP in patients with IBD in Korea. Methods: We investigated the incidence of PJP in patients with IBD and compared the characteristics of IBD patients with PJP episodes (IBD‐PJP group) with those of matched controls (IBD‐only group) using a large, well‐characterized referral center‐based cohort. Results: Among the 6803 IBD patients (3171 with Crohn's disease and 3632 with ulcerative colitis) enrolled in the Asan IBD Registry between June 1989 and December 2016, six patients (0.09%) were diagnosed with PJP. During the 57 776.0 patient‐years of follow‐up (median 7.2 years per patient), the incidence of PJP was 10.4 cases per 100 000 person‐years, and none of these patients had received PJP prophylaxis. In case–control analysis, the IBD‐PJP group (n = 6) showed significantly higher C‐reactive protein level at diagnosis of IBD (P = 0.006), as well as higher exposure to corticosteroids (P = 0.017), than did controls (n = 24). In addition, the IBD‐PJP group showed higher rates of double (50% vs 12.5%) or triple (33.3% vs 4.2%) immunosuppression than did controls, although these are not statistically significant. Conclusions: Although the incidence of PJP in Korean patients with IBD is low, careful monitoring is necessary for the early detection of PJP. In addition to the patients receiving double or triple immunosuppression, PJP prophylaxis should be considered especially in patients with severe disease activities requiring corticosteroids. [ABSTRACT FROM AUTHOR]

We aimed to develop a computer-aided diagnostic system (CAD) for predicting colorectal polyp histology using deep-learning technology and to validate its performance. Near-focus narrow-band imaging (NBI) pictures of colorectal polyps were retrieved from the database of our institution. Of these, 12480 image patches of 624 polyps were used as a training set to develop the CAD. The CAD performance was validated with two test datasets of 545 polyps. Polyps were classified into three histological groups: serrated polyp (SP), benign adenoma (BA)/mucosal or superficial submucosal cancer (MSMC), and deep submucosal cancer (DSMC). The overall kappa value measuring the agreement between the true polyp histology and the expected histology by the CAD was 0.614–0.642, which was higher than that of trainees (n = 6, endoscopists with experience of 100 NBI colonoscopies in <6 months; 0.368–0.401) and almost comparable with that of the experts (n = 3, endoscopists with experience of 2,500 NBI colonoscopies in ≥5 years) (0.649–0.735). The areas under the receiver operating curves for CAD were 0.93–0.95, 0.86–0.89, and 0.89–0.91 for SP, BA/MSMC, and DSMC, respectively. The overall diagnostic accuracy of the CAD was 81.3–82.4%, which was significantly higher than that of the trainees (63.8–71.8%, P < 0.01) and comparable with that of experts (82.4–87.3%). The kappa value and diagnostic accuracies of the trainees improved with CAD assistance: that is, the kappa value increased from 0.368 to 0.655, and the overall diagnostic accuracy increased from 63.8–71.8% to 82.7–84.2%. CAD using a deep-learning model can accurately assess polyp histology and may facilitate the diagnosis of colorectal polyps by endoscopists. [ABSTRACT FROM AUTHOR]

Background and Aim: The feasibility of endoscopic submucosal dissection (ESD) as a treatment option for dysplasia in ulcerative colitis (UC) has been reported, but the associated therapeutic decision‐making and clinical outcomes have not been extensively investigated. Methods: We retrospectively reviewed 25 UC patients who were referred for potential ESD of non‐polypoid or sessile dysplasia. We analyzed the treatment decisions and the ESD and colectomy outcomes for this patient group. Results: All lesions were located at the colitic segments. The median UC duration was 13.4 years. A colectomy was recommended for 10 patients because of ulceration with indistinct borders (one patient), non‐ulceration with indistinct borders (two patients), and non‐lifting signs (seven patients). The remaining 15 patients underwent ESD. The en bloc and R0 resection rates were 93.3% and 80%, respectively. The median hospitalization periods were 1 (range, 1–2) day after ESD and 7 (range, 5–30) days after colectomy. No procedure‐related complications occurred after ESD, but early and late postoperative complications occurred in two (22.2%) and six (66.7%) of the colectomized patients, respectively. Fourteen ESD cases were followed endoscopically for a median period of 24.7 (range, 5.2–64.8) months. Local recurrence occurred in 2 (14.3%) patients, and metachronous recurrence was identified in two separate patients (14.3%). Conclusions: Endoscopic submucosal dissection is a feasible endoscopic treatment option for UC‐associated dysplasia showing noninvasive pit or vascular patterns, no surface ulceration, distinct borders, and appropriate lifting after submucosal injection. Meticulous endoscopic surveillance is essential to monitor for local or metachronous recurrence of dysplasia after ESD. [ABSTRACT FROM AUTHOR]

Background and Aim: The risk and clinical impact of perianal disease (PAD) in ulcerative colitis (UC) patients have not been fully evaluated. We investigated the incidence of PAD in UC patients and compared clinical characteristics and outcomes of UC according to the presence of PAD. Methods: We performed a nationwide population‐based cohort study and a hospital‐based cohort study. Using the 2010–2014 data from the Korean National Health Insurance claims database, we calculated incidence rates and standardized incidence ratios of PAD in UC patients compared with the general population. We evaluated the clinical characteristics and outcomes of UC patients with PAD in both population‐based and hospital‐based cohorts. To reduce clinically meaningful confounding factors, we also conducted matched analyses. Results: In the population‐based cohort, the incidence rate and standardized incidence ratio of PAD in UC patients were 3.74/1000 person‐years (95% confidence interval, 3.25–4.31) and 2.88 (95% confidence interval, 2.50–3.32), respectively. In the hospital‐based cohort, the cumulative probabilities of PAD at 1, 5, 10, and 20 years after diagnosis were 1.0%, 2.3%, 4.0%, and 6.3%, respectively. In both population‐based and hospital‐based cohorts, UC patients with PAD showed higher proportions of corticosteroid use and extensive colitis at diagnosis. The requirements for anti‐tumor necrosis factor agents and colectomy were significantly higher in UC patients with PAD before and after matched analysis. Conclusions: The risk of PAD is higher in UC patients than in the general population. UC patients with PAD have distinct clinical features and poor outcomes, as indicated by the greater need for UC‐related medications and colectomy. [ABSTRACT FROM AUTHOR]

Background: Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinson's disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals.Methods: The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped.Results: In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70-20.97, P = 0.01). In an interaction analysis, SNP rs11931074-PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58-33.88, P = 0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS.Conclusion: This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein-Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS.Methods: The study included 58 patients with GCLS (29 EBV+ and 29 EBV−) who underwent curative resection. Expression of CD3, CD8, PD-1, and PD-L1 in tumor cells and TILs was analyzed using a quantitative multispectral imaging system (Opal™), with these results validated by immuno-histochemical assays for PD-L1 on whole slide sections.Results: The proportion of tumors overexpressing PD-L1 (31.0 vs. 0%, P = 0.002), TIL density (4548 vs. 2631/mm2, P < 0.001), and intra-tumoral CD8+ T-cell density (2650 vs. 1060/mm2, P < 0.001) were significantly higher in EBV+ than in EBV− GCLS. In addition, CD8+/CD3+ T-cell ratio was higher in EBV+ than in EBV− GCLS (55.3 vs. 35.8%, P < 0.001). Lower TIL density, defined as < 1350/mm2, was a significant negative factor of survival.Conclusions: Despite histopathological similarity, quantitative multispectral imaging revealed differences in the tumor immune micro-environment between EBV+ and EBV− GCLS, indicating that the underlying pathogenesis differs in these two disease entities. TIL density may be a prognostic marker in patients with GCLS. [ABSTRACT FROM AUTHOR]

Background: Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear.Aims: This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3' untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs).Methods: RNA-sequencing and small RNA-sequencing were performed on AGS and MKN-45 cells with a stable ADAR1 knockdown. Changed frequencies of editing and mRNA and miRNA expression were then identified by bioinformatic analyses. Targets of RNA editing were further validated in patients' samples.Results: In the Alu region of both gastric cell lines, editing was most commonly of the A-to-I type in 3'-UTR or intron. mRNA and protein levels of PHACTR4 increased in ADAR1 knockdown cells, because of the loss of seed sequences in 3'-UTR of PHACTR4 mRNA that are required for miRNA-196a-3p binding. Immunohistochemical analyses of tumor and paired normal samples from 16 gastric cancer patients showed that ADAR1 expression was higher in tumors than in normal tissues and inversely correlated with PHACTR4 staining. On the other hand, decreased miRNA-148a-3p expression in ADAR1 knockdown cells led to increased mRNA and protein expression of NFYA, demonstrating ADAR1's editing-independent function.Conclusions: ADAR1 regulates post-transcriptional gene expression in gastric cancer through both RNA editing-dependent and editing-independent mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the recurrence rate of colorectal neoplasia showing histologic lateral margin involvement after en bloc endoscopic submucosal dissection (ESD).Methods: We reviewed 527 colorectal lesions that were removed by en bloc ESD from 2005 to 2013 and followed by endoscopy. Based on the postprocedural pathologic reports, the lesions were categorized as follows: lesions with clear deep and positive lateral margins (n = 63) and lesions with R0 resection (n = 299).Results: The tumor size was 45.7 ± 21.1 mm in the lateral margin-positive group and 30.6 ± 15.1 in the R0 group (P < 0.001). Procedure time was longer in the lateral margin-positive group than in the R0 group (94.3 ± 75.1 vs. 54.1 ± 48.9 min; P < 0.001). Lateral margin positivity was associated with ESD time ≥ 120 min in the multivariate analysis. Compared with 0-I morphology, LST-G was significantly associated with the lateral margin positivity. The volume of ESD experience in endoscopists may also be associated with the lateral margin positivity. Histologic reassessment of the specimen suggested that 32.2% of lateral margin-positive cases based on the initial pathology report were false-positive lateral margin involvement. The 5-year cumulative recurrence rate was 0.6% in the R0 group and 5% in the margin-positive group (P = 0.198).Conclusions: The local recurrence rate was not higher in lateral margin-positive cases than in R0 resection cases if the colorectal epithelial neoplasia was removed in an en bloc manner using ESD. Meticulous pathologic interpretation may reduce unnecessarily frequent surveillance after en bloc ESD. [ABSTRACT FROM AUTHOR]

Background/Aims Fructose malabsorption (FM) mimics symptoms of irritable bowel syndrome (IBS), and its prevalence has increased. Diagnosing FM in IBS is challenging because of its overlap with small intestinal bacterial overgrowth (SIBO). We assessed the prevalence of FM by comparing patients with IBS with asymptomatic control individuals after excluding SIBO using the glucose hydrogen breath test (HBT). Methods Patients diagnosed with IBS and asymptomatic control individuals were enrolled prospectively. Dietary habits were assessed with the Food Frequency Questionnaire. After excluding SIBO, participants underwent HBTs with both 15 g and 25 g of fructose. Results Thirty-five patients with IBS and 35 age- and sex-matched asymptomatic control individuals were enrolled. The 15-g fructose HBT yielded positive results in 7 of the 35 (20.0%) patients with IBS and in 2 of 35 (5.7%) controls (P = 0.070). The 25-g fructose HBT was positive in 16 of the 35 (45.7%) patients with IBS and in 8 of the 35 (22.9%) controls (P = 0.040). Analysis of the Food Frequency Questionnaire responses showed no significant differences between the 2 groups in dietary intake, although patients with IBS showed a significantly higher mean fiber intake than controls (21.24 ± 11.35 g vs 15.87 ± 7.07 g, respectively, P = 0.040). Conclusions The 25-g fructose HBT identified FM in a significantly higher percentage of SIBO-negative patients with IBS than in asymptomatic control individuals, suggesting that FM may correlate with IBS. Education regarding dietary control of foods containing fructose may be useful for the management of patients with IBS. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the clinical characteristics and clinical course of Asian elderly-onset Crohn’s disease (EOCD) patients in a large well-defined cohort of South Korean IBD patients. Materials and methods: From the Asan inflammatory bowel disease registry, we identified 29 EOCD patients (diagnosed with CD in age of 60 years or over) out of 2989 CD patients (1.0%). After excluding two patients with unclear data, 27 EOCD were matched with 108 young-onset CD (YOCD) and 108 middle age-onset CD (MOCD) for the interval from symptom onset to diagnosis (±3 years) and follow-up duration (±3 years). Results: Females were predominant in the EOCD group (59.3%) compared to MOCD (31.5%) and YOCD (29.6%) groups (p = .012). In EOCD group, terminal ileal location was the most common (63.0%) at diagnosis, whereas ileocolonic location in other groups (57.4% in MOCD and 78.7% in YOCD, respectively) (p < .001). Patients with perianal fistula at CD diagnosis were less common (14.8% in EOCD vs. 28.7% in MOCD vs. 49.1% in YOCD, p < .001). During follow-up, thiopurines were used less frequently in the EOCD group (48.1% in EOCD vs. 87.0% in MOCD vs. 89.8% in YOCD, p < .001), but the risk for intestinal resection was comparable among three groups (p = .583). Conclusions: EOCD may have a better clinical course than MOCD and YOCD, as demonstrated by the similar risk for intestinal resection despite the less frequent use of thiopurines. [ABSTRACT FROM AUTHOR]

Abstract: A rapid and accurate molecular fluorescence imaging technique will greatly reduce cancer mortality by overcoming the detection limit of the naked eye in colonoscopy. Two imaging probes are reported that can be co‐used for colonoscopic diagnosis: a fluorescent molecular probe, cresyl violet–glutamic acid derivative, that ratiometrically switches between two fluorescent colors in response to the enzyme activity of λ‐glutamyltranspeptidase and an antibody quantum dot probe that is a conjugate of biocompatible AgInS2 quantum dot with matrix metalloproteinase 14 antibodies. Validity of the probes is confirmed using human colon cancer cell lines, ex vivo mouse model tissues, and patient tumor colon tissues in which the tumor lesions are well‐visualized in less than five minutes. Co‐application of the two probes onto fresh colon tissues affords accurate visualization of carcinomas and also hyperplasia and adenoma regions. Fresh human colon adenoma tissues are also valuated, where the two probes show complementary diagnoses of cancer. Two‐photon microscopy shows the time‐dependent depth profiles of the two probes. Both rapidly permeate and populate most at 10–20 µm from the surface. Extensive toxicity studies are performed for the two probes at cellular level and also at the organ level using a small animal model. [ABSTRACT FROM AUTHOR]

Background. Although immunomodulators are increasingly used in Crohn’s disease (CD), a significant number of gastroenterologists still use 5-aminosalicylate (5-ASA) in combination with azathioprine (AZA) or 6-mercaptopurine (6-MP); there is limited evidence regarding the benefit of concomitant 5-ASA with AZA/6-MP compared with AZA/6-MP monotherapy for the treatment of CD. Study Design. A total of 106 patients who received AZA/6-MP for more than 3 months between January 1991 and May 2014 were identified retrospectively. Each patient was matched with 3 randomly selected controls who were treated with concomitant therapy during the same period. Results. The cumulative probabilities of steroid use at 5 and 10 years were 24.9% and 75.8% in the 5-ASA + AZA/6-MP group and 31.2% and 87.8% in the AZA/6-MP group, respectively (P=0.187). The cumulative probabilities of anti-TNF use, resectional surgery, and disease-related hospitalization were comparable between the groups. The younger age and the use of lower doses of immunomodulators were associated with higher requirement of rescue therapy. Conclusions. This study did not demonstrate that the concomitant use of 5-ASA with AZA/6-MP showed the proof or effect in terms of steroid requirements, anti-TNF use, resectional surgery, or disease-related hospitalization compared with that of AZA/6-MP alone. [ABSTRACT FROM AUTHOR]

Background and Aim The aim of this study was to investigate the clinical characteristics and prognosis of patients with elderly onset ulcerative colitis (EOUC), a new growing subgroup of UC. Methods This study retrospectively analyzed 3060 South Korean UC patients diagnosed between 1977 and 2014. The clinical characteristics and prognosis of EOUC, defined as UC in those aged ≥ 60 years at diagnosis, were compared with those of non-EOUC (NEOUC). Results Among the 3060 patients, 226 were diagnosed with EOUC (7.4%, median age at diagnosis 65.9 years [interquartile range, 62.9-68.7 years], 58.4% male). The frequency of EOUC increased from 3.9% in the interval 1977-1999 to 9.7% in the interval 2008-2014 ( P < 0.001). There were more ex-smokers in the EOUC than in the NEOUC group (44.2% vs 19.9%, P < 0.001). In the EOUC group, extensive colitis at diagnosis, and the maximum extent thereof, was less than in the NEOUC group (13.7% vs 22.6%, P = 0.002, and 34.5% vs 42.5%, P = 0.011 , respectively). The 10-year cumulative colectomy rate was significantly higher in the EOUC than in the NEOUC group (12.6% vs 7.7%, P = 0.015). UC-related and all-cause mortality were higher in the EOUC than in the NEOUC group (3.5% vs 0.6%, P < 0.001, and 12.4% vs 1.8%, P < 0.001, respectively). Conclusion Elderly onset ulcerative colitis patients are likely to exhibit distinct features both at diagnosis and during follow-up. It is necessary to pay more attention to, and to conduct further studies on, this particular group of patients. [ABSTRACT FROM AUTHOR]

Background and Aim Smoking cessation is known to improve the course of Crohn's disease (CD). However, the factors associated with smoking cessation after CD diagnosis have not been well established. Methods Clinical characteristics and change in smoking status were evaluated in 445 current smokers at the time of CD diagnosis. Patients were classified into three subgroups based on their final smoking status and time of smoking cessation: non-quitters, quitters at diagnosis, and quitters during follow-up. Results The overall smoking cessation rate was 55.7% (248 of 445 patients). The diagnosis of CD was the main reason for quitting (41.5%, 103 of 248 patients). Smoking cessation at the time of CD diagnosis was associated with intestinal resection within 3 months from CD diagnosis (odds ratio [OR] 2.355, 95% confidence interval [CI] 1.348-4.116, P = 0.003), light smoking (OR 2.041, 95% CI 1.157-3.602, P = 0.014), and initiation of smoking before 18 years of age (OR 0.570, 95% CI 0.327-0.994, P = 0.047). Light smoking (OR 1.762, 95% CI 1.019-3.144, P = 0.043) and initiation of smoking before 18 years (OR 0.588, 95% CI 0.381-0.908, P = 0.017) were also associated with overall smoking cessation. Conclusion Quitters after CD diagnosis, including quitters at diagnosis and quitters during follow-up, had features distinct from those of non-quitters. Given the motivation at CD diagnosis, a detailed history of smoking habits should be taken and all current smokers should be encouraged to quit smoking at the time of CD diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Large-scale studies regarding the long-term outcomes of adalimumab (ADA) treatment in Asian patients with Crohn's disease (CD) are still scarce.Methods: We retrospectively analyzed the long-term outcomes of ADA treatment in Korean CD patients who commenced on scheduled ADA treatment at Asan Medical Center between November 2008 and July 2016. Clinical response was defined as maintaining ADA treatment without dose intensification (DI) and/or major abdominal surgery (MAS).Results: Of the 254 patients who received at least two doses of ADA at 2-week intervals as induction therapy, 250 patients (98.4%) showed an initial favorable response by week 4. Among responders, 243 patients were followed up for longer than 4 weeks and were included for further analysis. The median duration of ADA maintenance therapy was 19.4 months. At the last follow-up, 45 patients (18.5%) required DI after a median of 16.8 months and 31 (12.8%) required MAS after a median of 8.9 months. Finally, 161 patients (66.3%) were still receiving ADA without DI and/or MAS. The cumulative probability of maintaining ADA without DI and/or MAS was 81.1% at 1 year, and 36.5% at 5 years. Secondary loss of response to previous infliximab (P = 0.001) and elevated baseline C-reactive protein at starting ADA treatment (P = 0.008) were identified as independent predictors of a poor response to ADA treatment using multivariate regression analysis.Conclusions: The long-term outcome of ADA treatment in a real-life cohort of Korean patients with CD appears to be comparable to that reported in previously published Western studies. [ABSTRACT FROM AUTHOR]

Background:Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking. Study:We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX. Results:Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients’ preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04–2.37;p = .032). Conclusions:The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies. [ABSTRACT FROM AUTHOR]

Intestinal inflammation and mucosal damage in Crohn’s disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn’s disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8–8.0]), the Kaplan–Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245–2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003–2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Incidence of and risk factors for intestinal free perforation (FP) in patients with Crohn's disease (CD) are not established.Aim: To establish rate of and risk factors for FP in a large cohort of CD patients.Methods: Medical records of CD patients who visited Asan Medical Center from June 1989 to December 2012 were reviewed. After matching the FP patients to controls (1:4) by gender, year, and age at CD diagnosis, and disease location, their clinical characteristics were compared using conditional logistic regression analysis.Results: Among 2043 patients who were included in our study cohort, 44 patients (2.15%) developed FP over a median follow-up period of 79.8 months (interquartile range 37.3-124.6), with an incidence of 3.18 per 1000 person-years [95% confidence interval (CI) 2.37-4.28]. All 44 patients underwent emergency surgery, and eight patients underwent reoperation within 12 months (8/44, 18.2%). Multivariable-adjusted analysis revealed that anti-TNF therapy [odds ratio (OR), 3.73; 95% CI 1.19-11.69; p = 0.024] was associated with an increased risk of FP.Conclusions: The incidence of FP in a large cohort of Korean CD patients was 2.15%, which was similar to that in Western reports. Anti-TNF therapy could be risk factors for FP. [ABSTRACT FROM AUTHOR]

Although early treatment of Crohn’s disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503–3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449–2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209–2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094–5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment. [ABSTRACT FROM AUTHOR]

Background and Aim Limited data are available regarding mortality from inflammatory bowel disease in non-Caucasian populations. Herein, we evaluated overall and cause-specific mortality in a hospital-based cohort of Korean inflammatory bowel disease patients. Methods We determined mortality in 2414 Crohn's disease patients and 2798 ulcerative colitis patients diagnosed between 1977 and 2013. Standardized mortality ratios were calculated in several demographic and phenotypic subgroups. Results During the mean 9-year follow up, 114 patients died: 35 with Crohn's disease and 79 with ulcerative colitis. The overall standardized mortality ratios were 1.40 (95% confidence interval: 0.97-1.94) in Crohn's disease and 0.73 (0.58-0.91) in ulcerative colitis. In Crohn's disease, female sex, age < 30 years at diagnosis, disease duration > 10 years, ileocolonic disease at diagnosis, perianal fistula, intestinal resection, and ever-use of corticosteroids were associated with higher mortality. In ulcerative colitis, male sex, age ≥ 30 years at diagnosis, disease duration ≤ 5 years, proctitis at diagnosis, and no history of colectomy were associated with lower mortality, while primary sclerosing cholangitis was associated with higher mortality. In both Crohn's disease and ulcerative colitis, high mortality rates due to nonmalignant gastrointestinal causes (standardized mortality ratios: 4.59 and 2.32, respectively) and gastrointestinal malignancies (standardized mortality ratios: 16.59 and 3.45, respectively) were observed. Cardiovascular mortality was lower in ulcerative colitis (standardized mortality ratio: 0.47). Conclusions The overall mortality tended to be higher in Crohn's disease patients than in the general population; it was slightly lower in ulcerative colitis patients than in the general population. [ABSTRACT FROM AUTHOR]