Case-case genome-wide association analysis identifying genetic loci with divergent effects on Crohn's disease and ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.

Identification of shared loci associated with both Crohn's disease and leprosy in East Asians.

Genome-wide association studies (GWAS) of Crohn's disease (CD) in European and leprosy in Chinese population have shown that CD and leprosy share genetic risk loci. As these shared loci were identified through cross-comparisons across different ethnic populations, we hypothesized that meta-analysis of GWAS on CD and leprosy in East Asian populations would increase power to identify additional shared loci. We performed a cross-disease meta-analysis of GWAS data from CD (1621 cases and 4419 controls) and leprosy (2901 cases 3801 controls) followed by replication in additional datasets comprising 738 CD cases and 488 controls and 842 leprosy cases and 925 controls. We identified one novel locus at 7p22.3, rs77992257 in intron 2 of ADAP1, shared between CD and leprosy with genome-wide significance (P = 3.80 × 10-11) and confirmed 10 previously established loci in both diseases: IL23R, IL18RAP, IL12B, RIPK2, TNFSF15, ZNF365-EGR2, CCDC88B, LACC1, IL27, NOD2. Phenotype variance explained by the polygenic risk scores derived from Chinese leprosy data explained up to 5.28% of variance of Korean CD, supporting similar genetic structures between the two diseases. Although CD and leprosy shared a substantial number of genetic susceptibility loci in East Asians, the majority of shared susceptibility loci showed allelic effects in the opposite direction. Investigation of the genetic correlation using cross-trait linkage disequilibrium score regression also showed a negative genetic correlation between CD and leprosy (rg [SE] = -0.40[0.13], P = 2.6 × 10-3). These observations implicate the possibility that CD might be caused by hyper-sensitive reactions toward pathogenic stimuli.

Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.

Influence of endoscopists' expertise level on clinical outcomes after bridge-to-surgery stenting in obstructive colorectal cancer.

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.

Efficacy and safety of oral sodium sulfate tablet compared with 1-L polyethylene glycol plus ascorbate: a prospective, randomized, endoscopist-blinded trial.

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.

Impact of Sarcopenia on Clinical Course of Inflammatory Bowel Disease in Korea.

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.

Feasibility of moxifloxacin and proflavine dual fluorescence imaging for detecting gastrointestinal neoplastic lesions: A prospective study.

OBJECTIVES: High-contrast and high-resolution imaging techniques would enable real-time sensitive detection of the gastrointestinal lesions. This study aimed to investigate the feasibility of novel dual fluorescence imaging using moxifloxacin and proflavine in the detection of neoplastic lesions of the human gastrointestinal tract. METHODS: Patients with the colonic and gastric neoplastic lesions were prospectively enrolled. The lesions were biopsied with forceps or endoscopically resected. Dual fluorescence imaging was performed by using custom axially swept wide-field fluorescence microscopy after topical moxifloxacin and proflavine instillation. Imaging results were compared with both confocal imaging with cell labeling and conventional histological examination. RESULTS: Ten colonic samples (one normal mucosa, nine adenomas) from eight patients and six gastric samples (one normal mucosa, five adenomas) from four patients were evaluated. Dual fluorescence imaging visualized detail cellular structures. Regular glandular structures with polarized cell arrangement were observed in normal mucosa. Goblet cells were preserved in normal colonic mucosa. Irregular glandular structures with scanty cytoplasm and dispersed elongated nuclei were observed in adenomas. Goblet cells were scarce or lost in the colonic lesions. Similarity analysis between moxifloxacin and proflavine imaging showed relatively high correlation values in adenoma compared with those in normal mucosa. Dual fluorescence imaging showed good detection accuracies of 82.3% and 86.0% in the colonic and the gastric lesions, respectively. CONCLUSIONS: High-contrast and high-resolution dual fluorescence imaging was feasible for obtaining detail histopathological information in the gastrointestinal neoplastic lesions. Further studies are needed to develop dual fluorescence imaging as an in vivo real-time visual diagnostic method.

High Risk of Fractures Within 7 Years of Diagnosis in Asian Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: In this nationwide population-based study, we investigated the risk of vertebral and hip fractures in patients with inflammatory bowel disease (IBD). METHODS: Using data from the Korean National Health Insurance claims database gathered between 2007 and 2016, we calculated the incidence rate ratios (IRRs) of vertebral and hip fractures in patients with newly diagnosed IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis) compared with an age- and sex-matched control population (matching ratio, 1:10; n = 186,871). RESULTS: During a median follow-up period of 4.5 years, the incidence rate and IRR of vertebral and hip fractures in patients with IBD were 2.88 per 1000 person-years and 1.24 (95% CI, 1.08-1.42), respectively. The cumulative risk of vertebral and hip fractures in IBD patients was 0.6%, 1.4%, and 1.9% at 2, 5, and 7 years after diagnosis, respectively, and this risk of fracture in IBD patients was higher than that in matched controls (P = .002). The use of corticosteroids further increased the risk of fractures in IBD patients (IRR, 1.37; 95% CI, 1.13-1.65) compared with matched controls. The risk of fractures was significantly higher in patients with Crohn's disease (CD) (IRR, 1.56; 95% CI, 1.19-2.04) than in matched controls, and this risk remained higher in patients with CD without corticosteroid exposure (IRR, 1.62; 95% CI, 1.12-2.34). The risk of fracture increased with age and was particularly high in females and in those with comorbidities. CONCLUSIONS: The risk of fractures was significantly high in newly diagnosed IBD patients, especially in those with CD regardless of corticosteroid exposure.

Improved adenoma detection by a novel distal attachment device-assisted colonoscopy: a prospective randomized controlled trial.

BACKGROUND AND AIMS: WingCap (A&A Medical Supply LLC, Seongnam, South Korea) is a novel distal attachment device for colonoscopy that combines a cap and an existing mucosal exposure device, such as Endocuff Vision (Arc Medical Design Ltd, Leeds, UK) and AmplifEYE (Medivators Inc, Minneapolis, Minn, USA). We aimed to investigate whether WingCap-assisted colonoscopy can improve the adenoma detection rate (ADR) and adenoma per colonoscopy (APC) and simultaneously shorten cecal intubation time compared with standard colonoscopy. METHODS: We conducted a single-center, prospective, randomized controlled trial for outpatients aged ≥18 years undergoing colonoscopy. The primary outcome was ADR differences with the assistance of WingCap. Secondary outcomes were APC and other colonoscopy quality indicators, such as cecal intubation and withdrawal times. RESULTS: In total, 537 patients were randomized for WingCap-assisted or standard colonoscopy. Their mean age was 59.3 years, and 48.5% were men. ADR was significantly higher in the WingCap group than in the control group (37.2% vs 26.6%, P = .012). APC was greater with WingCap than with standard colonoscopy (.72 ± 1.34 vs .45 ± 0.97, P = .008), prominently for nonpedunculated (.65 ± 1.25 vs .42 ± .95, P = .015) and diminutive (.42 ± .94 vs .20 ± .64, P = .002) adenomas. With WingCap, ADR and APC significantly increased for beginner endoscopists, whereas a modest increase was seen for experienced endoscopists. There were no differences in cecal intubation and withdrawal times between the 2 arms. No serious adverse event was associated with the use of WingCap. CONCLUSIONS: WingCap-assisted colonoscopy was tolerable and efficacious for improving ADR and APC compared with standard colonoscopy, especially for nonpedunculated and diminutive adenomas and for beginner endoscopists. (Clinical trial registration number: KCT0005214.).

Immune profile by multiplexed immunohistochemistry associated with recurrence after chemoradiation in rectal cancer.

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.

Shift to a Younger Age and Regional Differences in Inflammatory Bowel Disease in Korea: Using Healthcare Administrative Data.

BACKGROUND: Research using healthcare administrative data with a validated algorithm can reveal the real-world data of rare diseases. AIMS: We investigated an accurate algorithm for detecting incident cases of inflammatory bowel disease (IBD) from healthcare data and analyzed the nationwide population-based epidemiological features in Korea. METHODS: Healthcare data from Songpa-Kangdong districts in Seoul were extracted from the National Health Insurance Service and analyzed to identify the best algorithm reflecting the cohort data. The most accurate criterion was applied to the entire database for further analysis. RESULTS: With the selected working criteria, 37,555 incident cases of IBD (Crohn's Disease [CD], 13,130; ulcerative colitis [UC], 24,425) were identified from 2005 to 2016. The male-to-female ratio was 2.5:1 for CD and 1.4:1 for UC. Over 12 years, the annual standardized incidence rate (SIR) per 100,000 people increased from 1.6 to 2.7 and 3.8 to 4.3 for CD and UC, respectively. The peak age at diagnosis of UC shifted from 55-59 years to 20-24 years, whereas that of CD shifted from 19 to 17 years. The SIR of CD was higher in metropolitan areas than in non-metropolitan areas. CONCLUSIONS: This nationwide population-based epidemiologic study of Korean IBD revealed a gradual increase in the incidence rates and a notable shift toward younger age at diagnosis. Males were predominant in both CD and UC. There was an urban-rural difference in the SIR of CD.

The Risk of Tuberculosis in Patients With Inflammatory Bowel Disease Treated With Vedolizumab or Ustekinumab in Korea.

The present study investigated the risk of active tuberculosis in patients with inflammatory bowel disease (IBD) treated with vedolizumab or ustekinumab, in actual clinical settings in a country with an intermediate tuberculosis burden. The medical records of 238 patients with IBD who received vedolizumab or ustekinumab were retrospectively reviewed at a tertiary referral center in South Korea. All patients had ≥ 3 months of follow-up duration and underwent a latent tuberculosis infection screening test before initiation of the administration of these drugs. Of the 238 patients enrolled, 181 had Crohn's disease, and 57 had ulcerative colitis. During the median 18.7 months of follow-up, active tuberculosis did not develop in any patient treated with vedolizumab or ustekinumab. Therefore, we concluded that the risk of tuberculosis appears to be low in patients with IBD treated with vedolizumab or ustekinumab in South Korea.

Sessile serrated lesions in patients with adenoma on index colonoscopy do not increase metachronous advanced adenoma risk.

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.

Long-Term Risks of Parkinson's Disease, Surgery, and Colorectal Cancer in Patients With Slow-Transit Constipation.

BACKGROUND & AIMS: Long-term outcomes of constipation have not been evaluated fully. We investigated the incidence of Parkinson's disease, constipation-related surgery, and colorectal cancer (CRC) in patients with constipation and slow-transit constipation (STC), followed up for up to 20 years. METHODS: We collected data from 2165 patients (33.1% men; median patient age, 54 y; median symptom duration, 5.0 y) with a diagnosis of constipation (based on Rome II criteria) who underwent an anorectal function test and a colonic transit time study, from 2000 through 2010, at a tertiary university hospital in Seoul, South Korea. The presence of STC was determined from colonic transit time. We used the Kaplan-Meier method to analyze and compare cumulative probabilities of a new diagnosis of Parkinson's disease or CRC according to the presence of STC. The patients were followed up until the end of 2019. RESULTS: During a median follow-up period of 4.7 years (interquartile range, 0.7-8.3 y), 10 patients underwent constipation-related surgery. The cumulative probabilities of constipation-related surgery were 0.7% at 5 years and 0.8% at 10 years after a diagnosis of constipation. Twenty-nine patients (1.3%) developed Parkinson's disease; the cumulative probabilities were 0.4% at 1 year, 1.0% at 5 years, and 2.6% at 10 years after a diagnosis of constipation. At 10 years, 1.3% of patients with STC required constipation-related surgery and 3.5% of patients with STC developed Parkinson's disease; in contrast, none of the patients without STC required constipation-related surgery (P = .003), and 1.5% developed Parkinson's disease (P = .019). In multivariate analysis, patient age of 65 years or older at the diagnosis of constipation (hazard ratio, 4.834; 95% CI, 2.088-11.190) and the presence of STC (hazard ratio, 2.477; 95% CI, 1.046-5.866) were associated independently with the development of Parkinson's disease. Only 5 patients had a new diagnosis of CRC during the follow-up period. The risk of CRC did not differ significantly between patients with vs without STC (P = .575). CONCLUSIONS: In a long-term follow-up study of patients with constipation in Korea, most patients had no severe complications. However, patients older than age 65 years with a new diagnosis of STC might be considered for Parkinson's disease screening.

Comparison of long-term recurrence-free survival between primary surgery and endoscopic resection followed by secondary surgery in T1 colorectal cancer.

BACKGROUND AND AIMS: We aimed to investigate whether endoscopic resection of T1 colorectal cancer (CRC) before surgery (secondary surgery) unfavorably affects long-term recurrence-free survival (RFS) compared with surgery without prior endoscopic resection (primary surgery). METHODS: We reviewed the medical records of patients who underwent radical surgery for T1 CRC with high-risk histologic features at a tertiary referral hospital in Korea between 2011 and 2016. The primary outcome was RFS. We performed 2 types of propensity score (PS) analyses to control for confounders. RESULTS: Of 852 patients, 388 underwent primary surgery and 464 secondary surgery. During the median follow-up period of 57.0 months (range, 41.0-63.0), cancer recurred in 18 patients (2.1%). The 5-year RFS rates did not differ between the primary and secondary surgery groups (97.0 vs 98.5%, P = .194). Further analyses of RFS rates according to nodal stages and number of high-risk histologic features showed no difference between groups. Moreover, RFS rates were not different between the groups after PS matching. In multivariable Cox proportional regression analysis, baseline serum carcinoembryonic antigen level was an independent risk factor for cancer recurrence (hazard ratio, 1.464; 95% confidence interval, 1.242-1.725; P < .001) but prior endoscopic resection of T1 CRC was not (P = .201). Both PS analyses consistently showed no increase in cancer recurrence risk in the secondary surgery group. CONCLUSIONS: Our data showed no additional cancer recurrence risk by endoscopic resection before surgery of T1 CRC with high-risk histologic features.

Prevalence and risk factors of bowel symptoms in Korean patients with ulcerative colitis in endoscopic remission: a retrospective study.

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.

Risk and characteristics of tuberculosis after anti-tumor necrosis factor therapy for inflammatory bowel disease: a hospital-based cohort study from Korea.

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.

Comparison of outcomes of cyclosporine A and infliximab for steroid-refractory acute severe ulcerative colitis.

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.

Risk factors for rebleeding in Crohn's disease patients with acute severe lower gastrointestinal bleeding: With special reference to the role of anti-tumor necrosis factor therapy.

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.