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Background/Aims: Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment. Methods: This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC. Results: Twenty-three patients met the inclusion criteria: 15 in group A and eight in group B. The serum infliximab levels significantly increased after SC switching in both groups. The electively switched group also exhibited increased infliximab levels after SC switching. Patients in group A showed improved partial Mayo score with a significant decrease in fecal calprotectin and C-reactive protein after switching. In group B, the fecal calprotectin level significantly decreased without clinical relapse after switching. A high proportion of patients (≥80%) in both groups achieved clinical and/or biochemical responses at the last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction. Conclusion : s: In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of better efficacy and safety.

Background/Aims The short- and long-term effects of adalimumab (ADA) on Korean patients with intestinal Behcet’s disease (BD) for remain unclear. Therefore, a multicenter study was performed to evaluate the efficacy and safety of ADA in Korean patients with intestinal BD in a real-world setting. Methods The medical records of 67 patients with BD prescribed ADA between January 2012 and December 2020 at five referral centers in Korea were retrospectively analyzed and the safety and efficacy of ADA within 52 weeks were assessed. To evaluate the clinical efficacy of ADA, the Disease Activity Index for Intestinal BD (DAIBD) and representative blood biochemical markers were compared at 0, 12, 24, and 52 weeks of ADA treatment. Results During the follow-up period of 52 weeks, 46 patients continued ADA treatment. The cumulative drug survival rate was 83.5%. The DAIBD score decreased over the study period (p < 0.001). Moreover, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum albumin levels significantly improved at 12, 24, and 52 weeks of ADA treatment (all, p

Background/Aims: Owing to the low prevalence of small-bowel adenocarcinoma (SBA), data on the impact of Crohn’s disease (CD) on the survival of patients with SBA are lacking. Therefore, we investigated this issue in this study. Methods: In this bicenter cohort study, patients with histologically confirmed SBA were retrospectively enrolled and classified into two groups: sporadic SBA and CD-associated SBA. Patients with duodenal SBA were excluded. Overall survival, disease-free survival, and factors associated with survival were analyzed. Results: Of 128 patients with SBA, 115 had sporadic SBA and 13 had CD-associated SBA. Ileal involvement and poorly differentiated tumors were more common in the CD-associated SBA group than in the sporadic SBA group (ileal involvement, 53.8% vs 22.6%; poor differentiation, 46.2% vs 14.8%; both p

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.

Total regression without endoscopic treatment of colorectal adenoma is rare. We report the case of a 58-year-old male diagnosed with advanced gastric cancer and advanced colorectal adenoma. He received chemotherapy for gastric cancer and achieved regression of colorectal adenoma. To our knowledge, this is the first case of regression of colorectal adenoma.

Tuberculosis is an adverse event in patients with Crohn’s disease receiving anti-tumor necrosis factor (TNF) therapy. However, tuberculosis presenting as a bronchoesophageal fistula (BEF) is rare. We report a case of tuberculosis and BEF in a patient with Crohn’s disease who received anti-TNF therapy. A 33-year-old Korean woman developed fever and cough 2 months after initiation of anti-TNF therapy. And the symptoms persisted for 1 months, so she visited the emergency room. Chest computed tomography was performed upon visiting the emergency room, which showed BEF with aspiration pneumonia. Esophagogastroduodenoscopy with biopsy and endobronchial ultrasound with transbronchial needle aspiration confirmed that the cause of BEF was tuberculosis. Anti-tuberculosis medications were administered, and esophageal stent insertion through endoscopy was performed to manage the BEF. However, the patient’s condition did not improve; therefore, fistulectomy with primary closure was performed. After fistulectomy, the anastomosis site healing was delayed due to severe inflammation, a second esophageal stent and gastrostomy tube were inserted. Nine months after the diagnosis, the fistula disappeared without recurrence, and the esophageal stent and gastrostomy tube were removed.

Abstract 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.

Background/Aims We investigated the real-world effectiveness and safety of ustekinumab (UST) as induction treatment for Koreans with Crohn’s disease (CD). Methods CD patients who started UST were prospectively enrolled from 4 hospitals in Korea. All enrolled patients received intravenous UST infusion at week 0 and subcutaneous UST injection at week 8. Clinical outcomes were assessed using Crohn’s Disease Activity Index (CDAI) scores at weeks 8 and 20 among patients with active disease (CDAI ≥150) at baseline. Clinical remission was defined as a CDAI

Background/Aims: Chronic enteropathy associated with SLCO2A1 gene (CEAS), an inherited disease characterized by nonspecific intestinal ulcers, has emerged in the Japanese population via loss-of-function mutations in the SLCO2A1 gene. We aimed to investigate the clinical and genetic characteristics of Korean patients diagnosed with CEAS. Methods: From July 2018 to July 2021, we performed Sanger sequencing of the SLCO2A1 gene in 46 patients with chronic intestinal ulcers. CEAS was confirmed based on known SLCO2A1 mutations. We summarized the clinical characteristics of patients with confirmed CEAS. Results: Fourteen out of 46 patients (30.4%) had genetically confirmed CEAS, and two SLCO2A1 variants were detected (splicing site variant c.940+1G>A and nonsense mutation [p.R603X] in SLCO2A1). Twelve patients (85.7%) were females and the median age at diagnosis of CEAS was 44.5 years. All patients presented with abdominal pain, and 13 patients (92.9%) presented with anemia (median hemoglobin, 9.6 g/dL). Ten patients (71.4%) had hypoalbuminemia (median, 2.7 g/dL). The most commonly involved site was the ileum (13/14, 92.9%). Manifestations of primary hypertrophic osteoarthropathy (PHO), such as digital clubbing, pachydermia, and periostosis were observed in five patients (28.6%) and two male patients and one female patient satisfied all major PHO diagnostic criteria. Conclusions: The clinical and genetic characteristics of Korean patients with confirmed CEAS were similar to those reported in the literature. CEAS should be considered in the differential diagnosis for patients with unexplained chronic nonspecific ulcers of the small intestine.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p

Background/Aims We aimed to investigate the oral beclomethasone dipropionate’s (BDP) efficacy as an add-on therapy and to clarify the predictive factor for response to oral BDP in Korean ulcerative colitis (UC) patients. Methods Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before BDP initiation were included. Partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a post-treatment pMS ≤ 1 point. Clinical response (CRES) was defined as an at least 2-point decrease in post-treatment pMS and an at least 30% decrease from baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Results Of all, 37 showed CREM, 19 showed CRES, and 44 were NRs. The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, p = 0.011) than NRs. In contrast to NRs, CREM and CRES patients showed significant improvement of post-treatment erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (ESR with p = 0.001, CRP with p = 0.004, respectively). Moreover, the initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with p < 0.001). In multivariate analyses, initial stool frequency subscore (SFS) of 0 and RBS of 0 were predictive factors for CREM (odds ratio [OR], 15.359; 95% confidence interval [CI], 1.085 to 217.499; p = 0.043 for SFS, and OR, 11.434; 95% CI, 1.682 to 77.710; p = 0.013 for RBS). Conclusions Oral BDP is an efficacious add-on therapy in Korean UC patients. Patients with initial SFS or RBS of 0 may be particularly good candidates for oral BDP.

Over the past decades, there has been a rapid increase in the incidence and prevalence of inflammatory bowel disease (IBD) in Asia. The natural history of IBD in Asian patients could be different from that in Western patients due to variations in disease phenotypes and genotypes as well as the healthcare environment between the 2 populations. To adequately cope with this disease, it is important to fully understand the potential differences in its natural history among different populations. In this review, we evaluated the differences in the clinical course of IBD between Asian and Western patients with regards to phenotypic progression, hospitalization, major surgery, risk of colorectal cancer, and mortality, mainly based on the results of population-based studies. The findings of our narrative review suggest that the clinical course of Asian patients with IBD, especially ulcerative colitis, is better than that of Western patients, as indicated by the lower rates of major surgery and hospitalization. In addition, similar to Western patients, the clinical course of Asian patients with IBD has been improving as evidenced by the decreasing rates of disease behavior progression (in Crohn’s disease), hospitalization, and major surgery.

Background/Aims: Anti-hepatitis B virus (HBV) therapy is required for patients with HBV infection receiving biologics because of the high risk of HBV reactivation. However, it is unclear when to start biologics after anti-HBV treatment. We investigated the risk of HBV reactivation according to the timing of biologics initiation after anti-HBV treatment in immune-mediated inflammatory disease (IMID) patients with HBV infection. Methods: We retrospectively evaluated the incidence of HBV reactivation in IMID patients who received biologics between July 2005 and April 2020. The patients were divided into two groups (within 1-week and after 1-week) according to the timing of biologics initiation after anti-HBV treatment. The cumulative probabilities and factors associated with HBV reactivation were evaluated. Results: A total of 60 hepatitis B surface antigen-positive patients with IMID received biologics (within 1-week group, n=23 [38%]; after 1-week group, n=37 [62%]). During a median follow-up of 34 months (interquartile range, 20 to 74 months), three patients (5%) developed HBV reactivation. In univariate analysis, the timing of biologics after anti-HBV treatment was not significantly associated with the risk of HBV reactivation (hazard ratio, 0.657; 95% confidence interval, 0.059 to 7.327; p=0.733). The cumulative probabilities of HBV reactivation did not significantly differ according to the timing of biologics (p=0.731). Conclusions: The risk of HBV reactivation was not significantly associated with the timing of biologics administration after anti-HBV treatment. Thus, biologics may be initiated early in patients with IMID undergoing treatment for HBV.

Background/Aims Fecal S100A12 (FS) and serum S100A12 (SS) have been reported as novel biomarkers that accurately reflect intestinal inflammation. We evaluated if FS and SS in comparison to fecal calprotectin (FC) are associated with poor future outcomes in clinically quiescent Crohn’s disease (CD) patients. Methods We prospectively enrolled 49 CD patients in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150 for the past 6 months). Patients were followed for a median period of 4.4 years (interquartile range [IQR], 4.3–4.5). The following outcomes were evaluated: clinical relapse, CD-related hospitalization, step-up of medical treatment, and CD-related intestinal resection. Cox proportional-hazard regression model was constructed to assess the association of baseline markers with time-to-event outcomes. Results The median levels of baseline FS, FC, and SS were 0.042 mg/kg (IQR, 0.005–0.179), 486.8 mg/kg (IQR, 203.5–886.8) and 1,398.2 ng/mL (IQR, 791.8–2,759.9), respectively. FS correlated with FC (r = 0.689), erythrocyte sedimentation rate (r = 0.524), C-reactive protein (r = 0.499), and albumin (r = –0.446), but not with CDAI (r = 0.045). Interestingly, increased FS (top quartile) was associated with a 4.9-fold increased rate of future CD-related hospitalization (P= 0.009) and a 2.8-fold increased rate of step-up of medical treatment (P= 0.032), whereas increased FC and SS were not. These findings remained significant after adjusting for age, sex, disease duration, current smoking, C-reactive protein, serum albumin, CDAI, and FC, individually. Conclusions In this pilot study, increased FS and not FC or SS, was significantly associated with increased rates of future CD-related hospitalization and step-up of medical treatment among CD patients in clinical remission.

Background: Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. Objective: To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. Design: This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Methods: Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. Results: A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Conclusions: Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Plain language summary Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.

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.

Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p

Background/Aims: Although pediatric ulcerative colitis (UC) has a different phenotype and clinical course than adult UC, its clinical features and outcomes are poorly defined, especially in Asian populations. This study investigated the clinical features and long-term outcomes of pediatric UC in a Korean population. Methods: We retrospectively analyzed 208 patients aged

Background/Aims Data on the immunoprotective status against measles, mumps, rubella, varicella zoster virus (VZV), hepatitis A virus (HAV), and Epstein-Barr virus (EBV) infection in patients with inflammatory bowel disease (IBD) are still lacking. Therefore, we investigated the seropositivity rates for viral infectious diseases and the associated factors in Korean patients with IBD. Methods In this retrospective cohort study, serum immunoglobulin G antibody positivity rates against measles virus, mumps virus, rubella virus, VZV, HAV, and EBV viral capsid antigen (VCA) were measured in patients with Crohn’s disease or ulcerative colitis (UC) who first visited the IBD clinic. Seropositivity rates and their associated factors were analyzed. Results Between January 2016 and December 2018, 263 patients were enrolled (male, 167 [67.3%]; UC, 134 [50.9%]). The median age at serological test was 30 years (interquartile range, 22 to 46). The seropositivity rates were 84.0%, 85.2%, 66.5%, 87.4%, 50.0%, and 93.7% for measles, mumps, rubella, VZV, HAV, and EBV, respectively. Younger age at serological test was associated with seronegative status for measles (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.88 to 0.96), VZV (aOR, 0.83; 95% CI, 0.74 to 0.93), and HAV (aOR, 0.93; 95% CI, 0.91 to 0.95). Furthermore, IBD type-UC was associated with seronegative status against VZV (aOR, 0.33; 95% CI, 0.11 to 0.99). Conclusions Seropositivity rates for common viral infectious diseases in Korean patients with IBD were similar to those of the general population. In the younger age group, protective immunity against measles, VZV, and HAV is required, with proper vaccination, as necessary.

Background/Aims: Recently, the treatment of Crohn’s disease (CD) has changed to a treat-to-target strategy, in which disease progression is prevented with early intervention. We analyzed the long-term evolution of nonstricturing, nonpenetrating (B1) disease at diagnosis and factors related to disease evolution in pediatric CD. Methods: We retrospectively analyzed 402 patients between 2000 and 2013 who were younger than 18 years and had B1 disease at CD diagnosis. The median follow-up was 6.1 years (range, 1 to 13 years). The cumulative probabilities of developing stricturing (B2) or penetrating (B3) disease and associations between risk factors and disease behavior evolution were evaluated. Results: Among the 402 patients, 75 (18.7%) had B2 or B3 disease by the final follow-up. The cumulative probabilities of disease behavior evolution were 18.3%, 34.3%, and 50.9% at 5, 10, and 13 years, respectively. Patients whose disease progressed had an increased risk of intestinal resection (hazard ratio [HR], 3.61; 95% confidence interval [CI], 2.25 to 6.03; p

Abstract 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

Background/Aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Methods: Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years. Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC. Conclusions: In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy.

Abstract 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

Background/Aims: Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting. Methods: Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively. Results: A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting. Conclusions: In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.

Abstract Background Perianal fistula is one of the most common complications in Crohn’s disease, and various medical and surgical treatments are being tried. The aim of this study was to compare the perianal fistula closure rates following treatment with anti-tumor necrosis factor (TNF) agents or autologous adipose tissue-derived stem cell (auto-ASC) transplantation with Crohn’s disease (CD). Methods CD patients who underwent seton placement for perianal fistula from January 2015 to December 2019 at a tertiary referral center were retrospectively reviewed. Patients were divided into two groups, one that received sequential treatments with anti-TNF agents (anti-TNF group) and the other that underwent auto-ASC transplantation (stem cell group). Clinical variables and fistula closure rates were compared in the two groups. Results Of the 69 patients analyzed, 39 were treated with anti-TNF agents and 30 underwent auto-ASC transplantation. Compared with the stem cell group, patients in the anti-TNF group were older (p=0.028), were more frequently male (p=0.019), had fistulas with more penetrating behavior (p=0.002), had undergone surgery more frequently (p=0.010), and had a shorter interval from seton placement to intended treatment (p

Background/Aims: Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. Methods: We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. Results: One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). Conclusions: The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer intake. A 29-year-old male with end-stage renal disease of IgA nephropathy on maintenance hemodialysis was admitted for diffuse alveolar bleeding and pneumonia. He presented with a low-grade fever and watery diarrhea tinged with blood. Initially, a Clostridioides difficile-associated diarrhea treatment was started with positive findings of Clostridioides difficile toxin and culture. Despite this, there was no improvement in the symptoms even with the appropriate antibiotic treatment. Computed tomography of the abdomen and pelvis revealed an occlusive mass in the rectum and secondary obstructive changes in the sigmoid colon. The initial suspicion was a malignancy or fungal infection. Sigmoidoscopy with a biopsy identified the mass as a lump of mucous material with the entire lumen covered with exudate. The subsequent histopathology examination revealed a colonic mucosal injury and characteristic ''fish scale"-like sevelamer crystals in the exudate. The diagnosis of a sevelamer-induced rectal ulcer was made. We report this case of a sevelamer-associated rectal ulcer of the sigmoid.

Abstract 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.

Purpose Carcinoma arising from Crohn disease (CD) is rare, and there is no clear guidance on how to properly screen for at-risk patients and choose appropriate care. This study aimed to evaluate the clinicopathological characteristics, treatment, and oncologic outcomes of CD patients diagnosed with colorectal cancer (CRC). Methods Using medical records, we retrospectively enrolled a single-center cohort of 823 patients who underwent abdominal surgery for CD between January 2006 and December 2015. CD-associated CRC patients included those with adenocarcinoma, lymphoma, or neuroendocrine tumors of the colon and rectum. Results Nineteen patients (2.3%) underwent abdominal surgery to treat CD-associated CRC. The mean duration of CD in the CD-associated CRC group was significantly longer than that in the benign CD group (124.7±77.7 months vs. 68.9±60.2 months, P = 0.006). The CD-associated CRC group included a higher proportion of patients with a history of perianal disease (73.7% vs. 50.2%, P = 0.035) and colonic location (47.4% vs. 6.5%, P = 0.001). Among 19 CD-associated CRC patients, 17 (89.5%) were diagnosed with adenocarcinoma, and of the 17 cases, 15 (88.2%) were rectal adenocarcinoma. On multivariable analyses for developing CRC, only colonic location was a risk factor (relative risk, 7.735; 95% confidence interval, 2.862–20.903; P = 0.001). Conclusion Colorectal malignancy is rare among CD patients, even among patients who undergo abdominal surgery. Rectal adenocarcinoma accounted for most of the CRC, and colonic location was a risk factor for developing CRC.

Abstract 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 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.

Background/Aims The efficacy and safety of vedolizumab in moderate-to-severely active Crohn’s disease (CD) were demonstrated in the GEMINI 2 study (NCT00783692). This post-hoc exploratory analysis aimed to assess the efficacy and safety of vedolizumab in the subgroup of patients from Asian countries. Methods During the induction phase (doses at day 1, 15), clinical remission, enhanced clinical response, and change in C-reactive protein at 6 weeks; during the maintenance phase, clinical remission, enhanced clinical response, glucocorticoid-free remission and durable clinical remission at 52 weeks, were the efficacy outcomes of interest. Efficacy and safety of vedolizumab compared to placebo were assessed in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) using descriptive analyses. Results During the induction phase, in Asian countries (n = 51), 14.7% of the vedolizumab-treated patients achieved clinical remission at week 6 compared to none with placebo (difference, 14.7%; 95% confidence interval, 15.8%–43.5%). In non-Asian countries (n = 317), the remission rate at week 6 with vedolizumab was 14.5%. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks and placebo were 41.7%, 36.4%, and 0%, respectively; while enhanced clinical response rates were 41.7%, 63.6%, and 42.9%, respectively. During induction, 39.7% of patients with vedolizumab experienced an adverse event compared to 58.8% of patients with placebo, and vedolizumab was generally well-tolerated. Conclusions This post-hoc analysis demonstrates the treatment effect and safety of vedolizumab in moderate-to-severely active CD in patients from Asian countries.

Abstract 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.

Background/Aims: Endoscopic diagnosis of dysplasia or colitic cancer in patients with ulcerative colitis (UC) is more challenging than that of colorectal neoplasia in non-colitic patients. We aimed to evaluate the accuracy of the endoscopic diagnosis of “nonpedunculated” dysplasia or colitic cancer in UC patients. Methods: Ten endoscopists from four countries were surveyed using photographs of 61 histologically confirmed dysplastic or non-dysplastic lesions retrieved from the UC registry database of Asan Medical Center. The participants provided their assessment based on the given photographs and their intention to perform biopsy. Results: The overall diagnostic performance of the 10 participants is summarized as follows: sensitivity of 88.2% (95% confidence interval [CI], 84.3% to 91.5%), specificity of 34.8% (95% CI, 29.1% to 40.8%), positive predictive value of 63.0% (95% CI, 60.8% to 65.2%), negative predictive value of 70.2% (95% CI, 62.7% to 76.6%), and accuracy of 64.6% (95% CI, 60.7% to 68.4%). The interobserver agreement on the intention to perform a biopsy was poor (Fleiss kappa=0.169). Of the three endoscopic characteristics of the lesions, including ulceration, distinctness of the borders, and pit patterns, only neoplastic pit patterns were significantly predictive of dysplasia (odds ratio, 3.710; 95% CI, 2.001 to 6.881). The diagnostic sensitivity and specificity of neoplastic pit patterns were 68.2% (95% CI, 63.0% to 73.2%) and 63.3% (95% CI, 57.3% to 69.1%), respectively. Conclusions: Diagnostic performance based on the endoscopist's intention to perform a biopsy for nonpedunculated potentially dysplastic lesions in UC patients was suboptimal according to this survey-based study.

Purpose Upper gastrointestinal (GI) tract involvement in Crohn disease (CD) is rare and effectiveness of surgical treatment is limited. The aim of this study was to evaluate characteristics and surgical outcomes of upper GI CD. Methods Medical records of 811 patients who underwent intestinal surgery for CD between January 2006 and December 2015 at a single institution were reviewed. Upper GI CD was defined by involvement of the stomach to the fourth portion of duodenum, with or without concomitant small/large bowel CD involvement according to a modification of the Montreal classification. Results We identified 24 patients (21 males, 3 females) who underwent surgery for upper GI CD. The mean age at diagnosis was 27 ± 12 years, the mean age at surgery was 33 ± 11 years, and the mean duration of CD was 73.6 ± 56.6 months. Fifteen patients (62.5%) had history of previous perianal surgery. Ten patients (41.7%) had duodenal or gastric stricture and 14 patients (58.3%) had penetrating fistula; patients with fistula were significantly more likely to develop complications (57.1% vs. 20.0%, P = 0.035). One patient with stricture had surgical recurrence. In seven patients with fistula, fistula was related to previous anastomosis. Patients with fistula had significantly longer hospital stays than those with stricture (16 days vs. 11 days, P = 0.01). Conclusion Upper GI CD is rare among CD types (2.96%). In patients with upper GI CD, penetrating fistula was associated with longer hospital stay and more complications.

Background/Aims: Studies on long-term outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking. Methods: We analyzed long-term outcomes of Korean UC patients treated with adalimumab at the Asan Medical Center, Seoul, Korea. Results: Between July 2013 and October 2018, adalimumab therapy was started in a total of 100 patients with UC (65 males [65.0%]; median age, 39.5 years [interquartile range, 23.3 to 49.8 years]; and median disease duration, 3.0 years [interquartile range, 1.0 to 7.0 years]). The median duration of adalimumab therapy was 13.5 months (interquartile range, 4.0 to 32.0 months). Eight of 100 patients (8.0%) received induction therapy only, four (4.0%) of whom ultimately underwent colectomy. Of 92 patients who received adalimumab maintenance therapy, 30 (30.0%) stopped adalimumab therapy due to loss of response, and one patient (1.0%) was lost to follow-up. Among the 92 patients who received adalimumab maintenance therapy, the cumulative proportions of patients remaining on adalimumab maintenance therapy were 70.0% at 1 year and 48.9% at 5 years. High partial Mayo score after 8 weeks of adalimumab therapy (hazard ratio [HR], 1.217; 95% confidence interval [CI], 1.040 to 1.425; p=0.014) and a history of exposure to two biologic agents before adalimumab therapy (HR, 4.722; CI, 1.033 to 21.586; p=0.045) were predictors of adalimumab discontinuation. Conclusions: Long-term outcomes of adalimumab therapy in Korean UC patients appear to be comparable to those in previously published Western studies. Furthermore, previous exposure to multiple biologic agents before adalimumab therapy and disease activity after 8 weeks of adalimumab therapy were predictors of adalimumab discontinuation.

Background/Aims The use of complementary and alternative medicine (CAM) is a global phenomenon, including inflammatory bowel disease (IBD) patients. We aimed to assess the change in prevalence and patterns of CAM use, and attitudes towards CAM over an 8-year time interval (2006 vs. 2014) among IBD patients in Korea. Methods A total of 221 IBD patients (CD=142, UC=79) were asked to complete a questionnaire regarding CAM at two time points: at enrollment (2006) and 8 years later (2014/2015). Results The proportion of patients ever using CAM increased significantly from 60.2% in 2006 to 79.6% in 2014 (P

Background/Aims PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). Methods OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. Results In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. Conclusions In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)

Background/Aims We aimed to investigate the proportion of and risk factors for residual cancer and/or lymph node metastasis after surgery was performed because of high-risk pathological features in endoscopic resection specimen of suspected superficial submucosal colorectal cancer (SSMC). Methods We reviewed medical records of 497 patients (58.8 ± 9.8 years, 331 males) undergoing endoscopic resection of suspected SSMC. High-risk pathological features included: deep submucosal cancer invasion ≥ 1,000 μm; positive lymphovascular and/or perineural invasion; poorly differentiated adenocarcinoma; and positive resection margin. We investigated the occurrence of additional surgery and residual cancer and/or lymph node involvement in the surgical specimen. Results En bloc resection was performed in 447 patients (89.9%). High-risk pathological features were detected in 372 patients (74.8%). Additional surgery was performed in 336 of 372 patients with high-risk pathological features. Of these, 47 surgical specimens (14.0%) showed residual cancer and/or lymph node metastasis. Piecemeal resection was more common in those with residual cancer and/or lymph node involvement than those without (9/47 [19.1%] vs. 24/289 [8.3%], P= 0.032). Positive resection margin was also significantly associated with positive residual cancer and/or lymph node involvement. As the number of high-risk pathological features increased, the risk of regional lymph node metastasis increased proportionally (P= 0.002). Conclusions High-risk pathological features were frequently detected after endoscopic resection of suspected SSMC while residual cancer and/or lymph node metastasis were not commonly present in the additional surgical specimen. Further optimized strategy for proper endoscopic management of suspected SSMC is necessary.

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.

Considering the risk of reactivation of latent tuberculosis infection (LTBI), not only before starting tumor necrosis factor inhibitors but also before non-TNF inhibitor therapy, LTBI screening is routinely recommended for patients with inflammatory bowel disease (IBD). However, data on the positive conversion of LTBI test results during non-TNF inhibitor therapy are scarce. Among IBD patients treated with vedolizumab and/or ustekinumab, a total of 91 patients who had negative baseline interferon-gamma release assay (IGRA) results, assessed by QuantiFERON®-TB Gold In-tube or QuantiFERON®-TB Gold Plus, were enrolled. Serial LTBI test results after starting non-TNF inhibitor therapy were collected, and patients' clinical characteristics were analyzed. Positive IGRA conversion was observed in six of 91 patients (6.6%). The cumulative IGRA conversion–free survival rates after starting therapy were 97.7% after 1 year and 86.7% after 2 years. Ulcerative colitis was more common among converters compared with non-converters (66.7 vs. 23.5%, P = 0.040). Among six converters, four had been treated with vedolizumab, one with ustekinumab, and the other with vedolizumab followed by ustekinumab. All six patients had been previously exposed to TNF inhibitors before non-TNF inhibitor therapy: five to infliximab and one to both infliximab and adalimumab. After positive IGRA conversion, none of the six converters developed active tuberculosis while maintaining non-TNF inhibitor therapy (median 6.8 months, range 0.4–32.1 months). Positive IGRA conversion among IBD patients treated with vedolizumab and/or ustekinumab appears to occur somewhat frequently, but its clinical implications remain to be elucidated.

Background/Aims The onset of inflammatory bowel disease (IBD) usually occurs at young age, and therefore, women IBD patients experience pregnancy during their disease progression. Recently, the use of anti-tumor necrosis factor-α (anti-TNF-α) has been rapidly increasing. The aim of this study was to evaluate pregnancy related outcomes in women with IBD who were treated with anti-TNF-α during pregnancy and immunity of their children. Methods Korean women with IBD who had been treated with anti-TNF-α during pregnancy had been enrolled. Medical records were reviewed and a survey was performed for each patient. For the patients who agreed on additional examination for their children, children’s growth, medical history and antibody to hepatitis B surface antigen (anti-HBs) titer were checked. Results All 18 patients had been diagnosed with Crohn’s disease. There was not any case of preterm delivery, low birth-weight infant, congenital anomaly, nor stillbirth. All 12 children had followed the regular vaccination schedule for hepatitis B and 4 of them showed negative results for anti-HBs. After the 1 booster vaccination, all children demonstrated seroconversion. Regarding live vaccines, 4 children had bacillus Calmette-Guerin and 4 had rotavirus vaccine before 6 months, without any specific side effects. Conclusions This was the first study of immunity of the children born from IBD women who had been treated with anti-TNF-α medication during their pregnancy. IBD women had comparable pregnancy outcomes with the general women population, suggesting that the disease activity rather than the administered medication would be more important in healthy pregnancy. Considering the history of vaccination and anti-HBs titers, immunity seems to be intact in the children.

BACKGROUND AND STUDY AIM: To develop a molecular imaging endoscopic system that eliminates tissue autofluorescence and distinguishes multiple fluorescent markers specifically on the cancerous lesions. METHODS: Newly developed multi-spectral fluorescence endoscope device has the potential to eliminate signal interference due to autofluorescence and multiplex fluorophores in fluorescent probes. The multiplexing capability of the multi-spectral endoscope device was demonstrated in the phantom studies and multi-spectral imaging with endoscopy and macroscopy was performed to analyze fluorescence signals after administration of fluorescent probe that targets cancer in the colon. Because of the limitations in the clinical application using rigid-type small animal endoscope, we developed a flexible channel insert-type fluorescence endoscope, which was validated on the colonoscopy of dummy and porcine model. RESULTS: We measured multiple fluorescent signals simultaneously, and the fluorescence spectra were unmixed to separate the fluorescent signals of each probe, in which multiple fluorescent probes clearly revealed spectral deconvolution at the specific targeting area in the mouse colon. The positive area of fluorescence signal for each probe over the whole polyp was segmented with analyzing software, and showed distinctive patterns and significantly distinguishable values: 0.46 ± 0.04, 0.39 ± 0.08 and 0.73 ± 0.12 for HMRG, CET-553 and TRA-675 probes, respectively. The spectral unmixing was finally demonstrated in the dummy and porcine model, corroborating the targeted multi-spectral fluorescence imaging of colon dysplasia. CONCLUSION: The multi-spectral endoscopy system may allow endoscopists to clearly identify cancerous lesion that has different patterns of various target expression using multiple fluorescent probes.

Background/Aims The Crohn’s and Colitis Knowledge (CCKNOW) score does not reflect updated knowledge relating to inflammatory bowel disease (IBD). The aim of this study was to develop, validate, and apply a novel tool to measure disease-related knowledge in IBD patients. Methods A questionnaire composed of 24 items regarding knowledge of IBD was developed: Inflammatory Bowel Disease Knowledge (IBD-KNOW). Discriminate ability of IBD-KNOW was validated in three occupational groups (14 doctors, 20 nurses, and 19 clerks). The CCKNOW and IBD-KNOW were administered to IBD patients. Factors affecting the level of IBD-related knowledge were analyzed. Results The median Inflammatory Bowel Disease Knowledge (IBD-KNOW) score was significantly different among the three groups for validation (22 doctors, 20 nurses, and five clerks; p < 0.001). The IBD-KNOW showed excellent internal consistency (Cronbach α = 0.952) and high correlation with CCKNOW (Spearman ρ = 0.827, p = 0.01). A total of 200 IBD patients (120 Crohn’s disease, 80 ulcerative colitis) completed questionnaires. Multivariate analysis showed that a higher IBD-KNOW score than the median was associated with hospitalization history (odds ratio [OR], 2.625; p = 0.003), high education level (OR, 2.498; p = 0.012), and information acquired from patient organization (OR, 3.305, p = 0.035). Conclusions The IBD-KNOW demonstrated excellent test characteristics. Hospitalization history, education level, and information acquired from patient organization play an important role in correct IBD-related knowledge.

Background/Aims: The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods: The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results: Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions: Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.

Background: Anti-tumor necrosis factor (TNF) agents are increasingly used for rheumatic diseases and inflammatory bowel disease (IBD), but are associated with the development of anti-TNF-induced lupus (ATIL). Nonetheless, few ATIL studies on non-Caucasian IBD patients exist. Here, we investigated the incidence, clinical features, and risk factors of ATIL in Korea. Methods: We retrospectively reviewed the medical records of IBD patients undergoing anti-TNF therapy at our tertiary IBD center between 2008 and 2020. ATIL was diagnosed as a temporal association between symptoms and anti-TNF agents, and the presence of at least one serologic and non-serologic American College of Rheumatology criterion. The risk factors for ATIL occurrence were assessed using multivariate Cox regression analysis. Results: Of 1362 IBD patients treated with anti-TNF agents, 50 (3.7%) ATIL cases were suspected, of which 14 (1.0%) received a definitive diagnosis. Arthritis and mucocutaneous symptoms were observed in 13 and 4 patients, respectively. All ATIL cases were positive for anti-nuclear and anti-dsDNA antibodies. Four patients (30.8%) improved while continuing anti-TNF therapy. At the final follow up, the ATIL group ( n = 14) had a lower IBD remission rate (30.8% versus 68.8%, p = 0.019) than the non-ATIL group ( n = 36). Ulcerative colitis and longer disease duration were associated with ATIL occurrence, with hazard ratios of 7.017 ( p = 0.005) and 1.118 ( p = 0.002), respectively. Conclusion: Although rare, ATIL is associated with poor treatment response to IBD in Korean patients. ATIL should be considered if arthritis and mucocutaneous symptoms develop during anti-TNF therapy for IBD.

Background and Aim. The prevalence of obesity is increasing globally as is the prevalence of inflammatory bowel disease (IBD). Herein, we sought to evaluate the characteristics and prognosis of IBD in patients with obesity. Methods. We retrospectively reviewed the medical records of IBD patients who visited Asan Medical center. We used a large, well-characterized referral center-based cohort. The clinical features of IBD patients with body mass index (BMI) over 30 and matched controls with BMI under 30 were compared. Results. Among the 6,803 IBD patients enrolled in the Asan IBD Registry between June 1989 and December 2016, we identified 16 patients with Crohn’s disease (CD) and 27 patients with ulcerative colitis (UC) whose BMI was over 30 at the time of diagnosis. Their clinical characteristics and course were compared with those of 64 and 108 matched patients with CD and UC, respectively. There were no significant differences in the risk of using steroids (hazards ratio (HR) = 0.633 and P=0.254), immunomodulators (HR = 0.831 and P=0.517), and anti-tumor necrosis factor (TNF) therapy (HR = 1.539 and P=0.351) and risk of bowel resections (HR = 1.858 and P=0.231) between CD patients with BMI over 30 and those with BMI under 30; similarly, UC patients did not show significant differences in the risk of using steroids (HR = 0.613 and P=0.145), immunomodulators (HR = 0.492 and P=0.111), anti-TNF therapy (HR = 0.385 and P=0.095), and risk of colectomy (HR = 0.262 and P=0.104). In the subgroup analysis, under-weight UC patients had a higher cumulative probability of needing steroids (HR = 0.2510 and P=0.042), needing immunomodulators (HR = 0.097 and P=0.014), and a higher risk of receiving colectomy (HR = 0.024 and P=0.019) than obese UC patients. Conclusions. Obese IBD patients with CD or UC did not show significantly different clinical features from nonobese IBD patients.

BackgroundExpression quantitative trait loci (eQTL) datasets have extensively been used to help interpret genome-wide association study signals. Most eQTL analyses have been conducted with populations of European ancestry.ObjectiveTo determine the most functionally relevant genes at the Crohn’s disease (CD) loci identified in genome-wide association studies (GWAS) involving Asian populations and to find novel disease-associated genes, we conducted an eQTL analysis.MethodseQTL analysis was performed using whole-blood RNA-sequencing of 101 Korean patients with CD. FastQTL was used for a pair-wise genome analysis of ∼ 6.5 M SNPs and ∼ 22 K transcripts.ResultsWe identified 135,164 cis-eQTL and 3,816 eGenes with a false discovery rate less than 0.05. A significant proportion of the genes identified in our study overlapped with those identified in previous studies. The significantly enriched pathways of these 3,816 eGenes included neutrophil degranulation and small molecule biosynthetic process. Integrated analysis of CD GWAS with Korean eQTL revealed two putative target genes, TNFSF15 and GPR35, at two previously reported loci, whereas TNFSF15 only with the whole blood data from the Genotype-Tissue Expression (GTEx) project, highlighting the utility of building a population-specific data set, even of modest size. The risk alleles of these genes were found to be associated with lower expression levels of TNFSF15 and GPR35, respectively. Our eQTL browser can be accessed at “http://asan.crohneqtl.com/”.ConclusionThis resource would be useful for studies that need to employ genome-wide association analyses involving Asian populations.