Effectiveness of Early Thiopurine Use in Korean Patients With Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) Study.

BACKGROUND: Thiopurines play an important role in the management of steroid-refractory and steroid-dependent ulcerative colitis. However, the effectiveness of the early use of thiopurines in ulcerative colitis remains controversial. MATERIALS AND METHODS: In this multicenter prospective cohort (MOSAIK) study, we divided patients with ulcerative colitis into those who underwent early (within 6 mo of diagnosis) and late (6 mo after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. RESULTS: Overall, 333 patients with moderate-to-severe ulcerative colitis were included. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.9% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3 to 2.0); the median maintenance dose was 1.1 mg/kg (0.3 to 2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis (P=0.712). The presence of extraintestinal manifestations (hazard ratio: 4.674, 95% CI: 1.210-18.061, P=0.025) independently predicted an increased risk of clinical relapse. CONCLUSIONS: Patients with ulcerative colitis who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

Impact of age at diagnosis on long-term prognosis in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: Although age at disease onset is considered to be a significant factor in the prognosis of Crohn's disease, little is known about its influence on the long-term prognosis of those with intestinal Behçet's disease (BD). This study aimed to evaluate the long-term clinical outcomes of patients with intestinal BD according to age of disease onset. METHODS: Patients diagnosed with intestinal BD at < 18, 18-60, and > 60 years of age were classified into early-onset, adult-onset, and late-onset groups, respectively. The influence of disease onset time on clinical prognosis, including specific medical requirements, BD-related intestinal surgery, hospitalization, and emergency room visits, was compared using the log-rank test in a large cohort of patients with intestinal BD. RESULTS: Among 780 patients, 21 (2.7%), 672 (86.2%), and 87 (11.1%) comprised the early-onset, adult-onset, and late-onset groups, respectively. Patients in the early-onset group were more likely to require immunosuppressants than those in the adult-onset group (P = 0.048). Nine (42.9%), 158 (23.5%), and 18 (20.7%) patients in the early-onset, adult-onset, and late-onset groups, respectively, underwent intestinal resection. The early-onset group exhibited a higher risk for intestinal resection than the late-onset (P = 0.043) and adult-onset (P = 0.030) groups. The late-onset group exhibited a higher risk for BD-related hospitalization than the adult-onset group (P = 0.023). CONCLUSIONS: Age at diagnosis affected the clinical course of intestinal BD, including intestinal surgery, hospitalization, and specific medical requirements. Different treatment strategies should be established according to age at diagnosis.

Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patients with Crohn's Disease: A Multicenter Observational Study.

BACKGROUND: Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn's disease (CD). METHODS: We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission. RESULTS: MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p < 0.001), and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037). CONCLUSIONS: MTX combination therapy with biologics was effective and tolerable in patients with CD.

Risk factors for post-polypectomy bleeding in patients with end-stage renal disease undergoing colonoscopic polypectomy.

BACKGROUND AND AIMS: Little is known about the risk factors of bleeding after colonoscopic polypectomy in patients with end-stage renal disease (ESRD). This study investigated the incidence and risk factors of post-polypectomy bleeding (PPB), including immediate and delayed bleeding, in patients with ESRD. METHODS: Ninety-two patients with ESRD who underwent colonoscopic polypectomy between September 2005 and June 2020 at a single tertiary referral center were included. The patients' medical records were retrospectively reviewed. Patient- and polyp-related factors associated with immediate PPB (IPPB) were analyzed using logistic regression analysis. Additionally, the optimal cutoff polyp size related to a significant increase in the risk of IPPB was determined by performing receiver operating characteristic (ROC) analysis and calculating the area under the ROC curve (AUC). RESULTS: In total, 286 polyps were removed. IPPB occurred in 24 (26.1%) patients and 46 (16.1%) polyps and delayed PPB occurred in 2 (2.2%) patients. According to multivariate analysis, the polyp size (> 7 mm), old age (> 70), and endoscopic mucosal resection (EMR) as the polypectomy method (EMR versus non-EMR) were found to be independent risk factors for IPPB. According to the Youden index method, the optimal cutoff polyp size to identify high-risk polyps for IPPB was 7 mm (AUC = 0.755; sensitivity, 76.1%; specificity, 69.6%). CONCLUSIONS: Colonoscopic polypectomy should be performed with caution in patients with ESRD, especially in those with the following risk factors: advanced age (> 70 years), polyp size > 7 mm, and EMR as the polypectomy method.

Long-term clinical outcomes of intestinal Behçet's disease: A 30-year cohort study at a tertiary hospital in South Korea.

BACKGROUND AND AIM: We aimed to identify the long-term clinical outcomes of and prognostic factors for intestinal Behçet's disease (BD). METHODS: A cohort of 780 patients with intestinal BD between 1997 and 2021 was investigated to determine long-term clinical outcomes and prognostic factors at an inflammatory bowel disease clinic at Severance Hospital, Seoul, Korea. RESULTS: During the median follow-up period of 12.7 ± 7.2 years, 5-aminosalicylic acids, corticosteroids, immunomodulators, and anti-tumor necrosis factor-alpha (TNF-α) agents were required in 94.9%, 67.2%, 43.8%, and 14.6% of the patients, respectively. The cumulative rates of anti-TNF-α use were 3.7%, 7.5%, 8.5%, 12.1%, 17.6%, and 24.0%, and those for abdominal surgery were 5.7%, 10.9%, 12.6%, 16.5%, 21.6%, and 28.3%, at 1, 3, 5, 10, 20, and 30 years, respectively, after initial diagnosis of intestinal BD. The cumulative rates of hospitalization were 11.8%, 21.9%, 27.9%, 38.8%, 54.4%, and 74.8%, and those of emergency room visits were 10.0%, 19.8%, 22.7%, 31.6%, 50.0%, and 65.0% at 1, 3, 5, 10, 20, and 30 years. Older age at primary diagnosis, previous appendectomy history, higher disease activity index for intestinal Behçet's disease score, systemic BD, multiple intestinal ulcers, deep intestinal ulcers, higher C-reactive protein, lower hemoglobin, and lower albumin levels were associated with poor prognosis. Married status, higher body mass index, oral ulceration, and arthritis were negatively associated with poor prognosis. CONCLUSIONS: Data on the long-term clinical outcomes of intestinal BD and their prognostic factors could guide physicians in patient monitoring and in optimizing individualized treatment.

Application of Multigene Panel Testing in Patients With High Risk for Hereditary Colorectal Cancer: A Descriptive Report Focused on Genotype-Phenotype Correlation.

BACKGROUND: The genetic test solely based on the clinical features of hereditary colorectal cancer has limitations in clinical practice. OBJECTIVE: This study aimed to analyze the results of comprehensive multigene panel tests based on clinical findings. DESIGN: This was a cross-sectional study based on a prospectively compiled database. SETTING: The study was conducted at a tertiary hospital. PATIENTS: A total of 381 patients with high risk for hereditary colorectal cancer syndromes were enrolled between March 2014 and December 2019. MAIN OUTCOME MEASURES: The primary outcome was to describe the mutational spectrum based on genotype-phenotype concordance and discordance. RESULTS: Germline mutations were identified in 89 patients for polyposis hereditary colorectal cancer genes (76 in APC; 4 in PTEN; 4 in STK11; 3 in BMPR1A; 1 in POLE; 1 in POLD1), 89 patients for nonpolyposis hereditary colorectal cancer genes (41 in MLH1; 40 in MSH2; 6 in MSH6; and 2 in PMS2), and 12 patients for other cancer predisposition genes (1 in ATM; 2 in BRCA1; 1 in BRCA2; 1 in BRIP1; 1 in MLH3; 1 in NBN; 1 in PMS1; 1 in PTCH1; 1 in TP53; and 2 in monoallelic MUTYH). If we had used direct sequencing tests of 1 or 2 major genes based on phenotype, 48 (25.3%) of 190 mutations would not have been detected due to technical differences (12.1%), less frequent genotype (4.2%), unclear phenotype (3.7%), and genotype-phenotype discordance (4.7%). The genotype-phenotype discordance is probably linked to compound heterozygote, less distinctive phenotype, and insufficient information for colorectal cancer risk. LIMITATIONS: This study included a small number of patients with insufficient follow-up duration. CONCLUSIONS: A comprehensive multigene panel is expected to identify more genetic mutations than phenotype-based direct sequencing, with special utility for unclear phenotype or genotype-phenotype discordance. See Video Abstract at http://links.lww.com/DCR/B844. APLICACIN DE PRUEBAS DE PANEL MULTIGNICO EN PACIENTES CON ALTO RIESGO DE CNCER COLORRECTAL HEREDITARIO INFORME DESCRIPTIVO ENFOCADO EN LA CORRELACIN GENOTIPOFENOTIPO: ANTECEDENTES:La prueba genética basada únicamente en la característica clínica del cáncer colorrectal hereditario tiene limitaciones en la práctica clínica.OBJETIVO:Este estudio tuvo como objetivo analizar el resultado de pruebas integrales de panel multigénico basadas en hallazgos clínicos.DISEÑO:Este fue un estudio transversal basado en una base de datos recopilada prospectivamente.AJUSTE:El estudio se realizó en un hospital terciario.PACIENTES:Se inscribió un total de 381 pacientes con alto riesgo de síndromes de cáncer colorrectal hereditario entre marzo del 2014 y diciembre del 2019.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue describir el espectro mutacional basado en la concordancia y discordancia genotipo-fenotipo.RESULTADOS:Se identificaron mutaciones de la línea germinal en 89 pacientes para genes de cáncer colorrectal hereditario con poliposis (76 en APC; 4 en PTEN; 4 en STK11; 3 en BMPR1A; 1 en POLE; 1 en POLD1), 89 pacientes para genes de CCR hereditario sin poliposis (41 en MLH1; 40 en MSH2; 6 en MSH6; y 2 ​​en PMS2) y 12 pacientes por otro gen de predisposición al cáncer (1 en ATM; 2 en BRCA1; 1 en BRCA2; 1 en BRIP1; 1 en MLH3; 1 en NBN; 1 en PMS1; 1 en PTCH1; 1 en TP53; y 2 ​​en MUTYH monoalélico). Si hubiéramos utilizado pruebas de secuenciación directa de uno o dos genes principales basados ​​en el fenotipo, 48 (25,3%) de 190 mutaciones no se habrían detectado debido a diferencias técnicas (12,1%), genotipo menos frecuente (4,2%), fenotipo poco claro (3,7%) y discordancia genotipo-fenotipo (4,7%). La discordancia genotipo-fenotipo probablemente esté relacionada con el heterocigoto compuesto, el fenotipo menos distintivo y la información insuficiente para el riesgo de cáncer colorrectal.LIMITACIONES:Este estudio incluyó una pequeña cantidad de pacientes con una duración de seguimiento insuficiente.CONCLUSIONES:Se espera que un panel multigénico completo identifique más mutaciones genéticas que la secuenciación directa basada en el fenotipo, con especial utilidad para la discordancia de fenotipo o genotipo-fenotipo poco clara. Consulte Video Resumen en http://links.lww.com/DCR/B844. Traducción- Dr. Francisco M. Abarca-Rendon).

Comparative effectiveness of second-line biological therapies for ulcerative colitis and Crohn's disease in patients with prior failure of anti-tumour necrosis factor treatment.

BACKGROUND: Therapeutic options for inflammatory bowel disease (IBD) have increased since the introduction of tumour necrosis factor (TNF) inhibitors a few decades ago. However, direct comparisons of the effectiveness of second-line biological agents in patients with ulcerative colitis (UC) and Crohn's disease (CD) are lacking. METHODS: Patients with UC or CD who experienced anti-TNF treatment failure and subsequently used vedolizumab, ustekinumab, or tofacitinib as a second-line drug were retrospectively recruited. The primary outcomes were the clinical remission rate at week 16 and the cumulative relapse rate 48 weeks after receiving induction therapy. RESULTS: A total of 94 patients with UC or CD experienced anti-TNF treatment failure and received vedolizumab (UC: 37; CD: 28), ustekinumab (CD: 16), or tofacitinib (UC: 13). The clinical remission rates were not significantly different between the vedolizumab and tofacitinib groups in UC patients (56.8% vs. 46.2%, p = 0.509). In CD patients, the clinical remission rates were not significantly different between the vedolizumab and ustekinumab groups (53.6% vs. 50.0%, p = 0.820). Moreover, the cumulative rates of clinical relapse were not significantly different between the vedolizumab and tofacitinib groups in UC patients and between the vedolizumab and ustekinumab groups in CD patients (p = 0.396 and p = 0.692, respectively). Safety profiles were also similar among the treatment groups in both UC and CD patients. CONCLUSIONS: After prior anti-TNF therapy failure, vedolizumab and tofacitinib in UC patients and vedolizumab and ustekinumab in CD patients were not significantly different in terms of the efficacy in inducing and maintaining a clinical response.

IL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor.

Interaction between a tumor and its microenvironment is important for tumor initiation and progression. Cancer stem cells (CSCs) within the tumor interact with a microenvironmental niche that controls their maintenance and differentiation. We investigated the CSC-promoting effect of factors released from myofibroblasts into the microenvironment of early colorectal cancer tumors and its molecular mechanism. By messenger RNA microarray analysis, expression of HES1, a Notch signaling target, significantly increased in Caco-2 cells cocultured with 18Co cells (pericryptal myofibroblasts), compared to its expression in Caco-2 cells cultured alone. Caco-2 cells cultured in 18Co-conditioned media (CM) showed a significant increase in CD133+CD44+ cells and HES1 expression compared to that in Caco-2 cells cultured in regular media. Significant amounts of interleukin-6 (IL-6) and IL-8 were detected in 18Co-CM compared to levels in regular media. The 18Co-CM-induced increase in CD133+CD44+ cells was attenuated by IL-6- and IL-8-neutralizing antibodies. Furthermore, these neutralizing antibodies and inhibitors of STAT3 and gamma-secretase reduced the expression of HES1 induced in Caco-2 cells cultured in 18Co-CM. Immunohistochemical analysis of human tissues revealed that IL-6, IL-8, and HES1 expression increased from normal to adenoma, and from adenoma to cancer tissues. In addition, IL-6 and HES1 expression was positively correlated in early colorectal cancer tissues. In conclusion, the increase of CSCs by myofibroblasts could be mediated by IL-6/IL-8-induced HES1 activation in the tumor microenvironment. Based on these data, the IL-6/IL-8-mediated Notch/HES1 and STAT3 pathway, through which CSCs interact with their microenvironment, might be a potential target for the prevention and treatment of colorectal tumors.

Comparison of the Efficacy of Polaprezinc Plus Proton Pump Inhibitor and Rebamipide Plus Proton Pump Inhibitor Treatments for Endoscopic Submucosal Dissection-induced Ulcers.

GOALS: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. BACKGROUND: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. STUDY: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. RESULTS: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). CONCLUSION: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

Incidence and risk factors of micronutrient deficiency in patients with IBD and intestinal Behçet's disease: folate, vitamin B12, 25-OH-vitamin D, and ferritin.

BACKGROUND: Patients with inflammatory bowel disease (IBD) and intestinal Behçet's disease (BD) are vulnerable to micronutrient deficiencies due to diarrhea-related gastrointestinal loss and poor dietary intake caused by disease-related anorexia. However, few studies have investigated the incidence and risk factors for micronutrient deficiency. METHODS: We retrospectively analyzed 205 patients with IBD who underwent micronutrient examination, including folate, vitamin B12, 25-OH-vitamin D, and/or ferritin level quantification, with follow-up blood tests conducted 6 months later. RESULTS: Eighty patients (39.0%), who were deficient in any of the four micronutrients, were classified as the deficiency group, and the remaining 125 (61.0%) were classified as the non-deficient group. Compared to those in the non-deficiency group, patients in the deficiency group were much younger, had more Crohn's disease (CD) patients, more patients with a history of bowel operation, and significantly less 5-amino salicylic acid usage. Multivariate analysis revealed that CD and bowel operation were significant independent factors associated with micronutrient deficiency. CONCLUSIONS: The incidence of micronutrient deficiency was high (39.0%). Factors including CD, bowel operation, and younger ages were found to be associated with higher risks of deficiency. Therefore, patients with IBD, especially young patients with CD who have undergone bowel resection surgery, need more attention paid to micronutrition.

Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. METHODS: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/µL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/µL. RESULTS: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22-0.81; P = .009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P = .008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P < .001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. CONCLUSIONS: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.

Nationwide validation study of diagnostic algorithms for inflammatory bowel disease in Korean National Health Insurance Service database.

BACKGROUND AND AIM: We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database. METHOD: Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)-10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD-specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart-based diagnosis). A multiple sampling test verified the validation results from the entire study population. RESULTS: A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD-10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91-94.7]; specificity, 98.1% [96.9-98.8]; positive predictive value, 97.5% [96.1-98.5]; negative predictive value, 94.5% [92.8-95.8]) with the lowest error rate (4.2% [3.3-5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P-value < 0.05. CONCLUSIONS: We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database.

Outcomes and Management Strategies for Capsule Retention: A Korean Capsule Endoscopy Nationwide Database Registry Study.

BACKGROUND: The most concerning complication of capsule endoscopy (CE) is capsule retention (CR) in the gastrointestinal (GI) tract; however, the clinical outcomes and management of patients with CR are still uncertain. AIMS: This study aimed to investigate the clinical outcomes and management of CR. METHODS: The outcomes of CR in multiple centers between October 2002 and June 2018 were retrospectively reviewed. Data on CE indication, findings, and management details were analyzed. RESULTS: A total of 2705 consecutive small-bowel CE procedures were performed. CR was detected in 20 cases (0.7%). The most common site of CR was the small bowel (19 cases), followed by the esophagus (one case). In patients who underwent CE, CR was detected in nine (0.6%) of 1397 patients with obscure GI bleeding. Further, CR occurred in 11 (6.5%) of 169 patients with Crohn's disease based on the final diagnoses after CE. Capsule retrieval was safely performed surgically in nine cases and endoscopically in six cases. The retained capsules dislodged after steroid treatment in two cases, whereas three cases of CR resolved without any intervention. In multivariate analysis, the development of abdominal symptoms after CR was a significant predictive factor for requiring endoscopic or surgical interventions for capsule extraction. CONCLUSIONS: This large multicenter study shows that CR is a rare complication with favorable clinical outcomes. Three-fourths of the patients with CR were managed with endoscopic or surgical intervention, which was required particularly in patients with abdominal symptoms after CR.

Clinical outcomes and factors related to colonic perforations in patients receiving self-expandable metal stent insertion for malignant colorectal obstruction.

BACKGROUND AND AIMS: Although colonic perforation is a dreadful adverse event associated with stent placement, data on this topic are sparse. We aimed to investigate the clinical outcomes of colonic perforation and factors related to its occurrence in patients who received self-expandable metal stents (SEMSs) for malignant colorectal obstruction. METHODS: We retrospectively reviewed the data of 474 patients with malignant colorectal obstruction who received endoscopic SEMS insertion from April 2004 to May 2011 in Severance Hospital and Gangnam Severance Hospital. Early perforation, defined as perforation occurring within 2 weeks, was assessed in bridge-to-surgery (n = 164) and palliative stent placement patient groups (n = 310). Delayed perforation was analyzed using data from the palliative stent placement group alone. RESULTS: The technical and clinical success rates were 90.5% and 81.0%, respectively. Early and delayed perforations occurred in 2.7% (13/474) and 2.7% (8/301) of patients, respectively. Among 21 patients with perforation, 14 (66.7%) received emergency surgery and 5 (23.8%) died within 30 days after perforation. Regarding the perforation-related factors, age ≥70 years (odds ratio, 3.276; 95% confidence interval [CI], 1.041-10.309) and sigmoid colonic location (odds ratio, 7.706; 95% CI, 1.681-35.317) were independently associated with occurrence of early perforation. Stent location in the flexure (hazard ratio, 17.573; 95% CI, 2.004-154.093) and absence of peritoneal carcinomatosis (hazard ratio, 6.139; 95% CI, 1.150-32.776) were significantly associated with delayed perforation. CONCLUSIONS: The perforation-related 30-day mortality rate was 23.8%. Older age and sigmoid colonic location were significantly associated with occurrence of early perforation, whereas flexure location and absence of peritoneal carcinomatosis were related to delayed perforation.

Impact of peritoneal carcinomatosis on clinical outcomes of patients receiving self-expandable metal stents for malignant colorectal obstruction.

BACKGROUND: Peritoneal carcinomatosis can influence clinical outcomes of patients receiving self-expandable metal stents (SEMS) for malignant colorectal obstruction, but data regarding this issue are sparse. We analyzed the clinical outcomes of post-SEMS insertion for malignant colorectal obstruction based on carcinomatosis status. METHODS: Stent- and patient-related clinical outcomes were compared for carcinomatosis status in a retrospective review involving 323 consecutive patients (colorectal cancer 198 patients; extracolonic malignancy 125 patients) who underwent palliative SEMS placement for malignant colorectal obstruction from January 2005 to March 2012. Severity of carcinomatosis was classified as mild, moderate, or severe. RESULTS: Carcinomatosis was observed in 190 patients (58.8 %). The rates of technical (84.7 vs. 94.7 %; P = 0.005) and clinical (73.2 vs. 83.5 %; P = 0.03) success were lower in patients with vs. without carcinomatosis. Rates of early (2.1 % vs. 3.0 %; P = 0.72) and delayed (1.6 % vs. 6.0 %; P = 0.08) perforation and stent failure (27.9 % vs. 26.3 %; P = 0.75) showed no difference. Technical and clinical success rates were significantly different based on the severity of carcinomatosis (technical success rate: mild 90.7 %, moderate 97.4 %, severe 76.3 %, P = 0.003; clinical success rate: mild 83.3 %, moderate 82.1 %, severe 63.9 %, P = 0.01). In multivariate analysis, severe carcinomatosis was identified as an independent factor related to technical (odds ratio [OR] 0.18, 95 % confidence interval [CI] 0.06 - 0.56) and clinical (OR 0.33, 95 %CI 0.15 - 0.74) success. CONCLUSIONS: Peritoneal carcinomatosis was associated with decreased technical and clinical success rates in patients receiving SEMS for malignant colorectal obstruction. Moreover, the presence of severe carcinomatosis was an independent factor determining these clinical outcomes.

The association between Helicobacter pylori infection and the risk of advanced colorectal neoplasia may differ according to age and cigarette smoking.

BACKGROUND: The association between Helicobacter pylori infection and advanced colorectal neoplasia (ACN) remains controversial. This study aimed to clarify the association between H. pylori infection and ACN according to age groups. METHODS: We retrospectively analyzed the association between H. pylori infection and ACN in patients aged <50 and ≥50 years receiving a health checkup that included colonoscopy. Helicobacter pylori positivity was determined by the results of serum anti-H. pylori immunoglobulin G or rapid urease test, if the anti-H. pylori immunoglobulin G was in the borderline range. RESULTS: Among the 19 337 patients who were included, 56.2% and 3.4% were positive for H. pylori and ACN, respectively. Helicobacter pylori infection independently increased the risk of ACN in patients aged <50 years (odds ratio [OR], 1.602; 95% confidence intervals [CI], 1.194-2.150) but not in patients aged ≥50 years (OR, 1.046; 95% CI, 0.863-1.268). The positive association between H. pylori infection and ACN was affected by smoking history. When stratified by age and smoking history, H. pylori infection conferred an increased risk of ACN in patients aged <50 years with a history of smoking (OR, 1.926; 95% CI, 1.336-2.775) but not in the other 3 groups (3-way interaction test P = .023). Among patients aged <50 years with ACN, ACN in the left colon was found more frequently in patients with H. pylori infection and a history of smoking than in those without (69.3% vs 54.4%, respectively; P = .031). CONCLUSIONS: Helicobacter pylori infection confers an increased risk of ACN, but the association may differ according to age and smoking history.

Risk factors and clinical courses of concomitant primary sclerosing cholangitis and ulcerative colitis: a Korean multicenter study.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a rare progressive cholestatic liver disease of unknown causes, but is strongly associated with inflammatory bowel diseases (IBDs), particularly ulcerative colitis (UC). However, studies comparing risk factors and clinical courses of patients with concomitant UC and PSC with those of patients with PSC alone are lacking. METHODS: We retrospectively reviewed patients with PSC diagnosed between 2005 and 2017 in four tertiary hospitals in Korea. We compared the risk factors and outcomes of concomitant UC and PSC (UC-PSC) and those of PSC alone. RESULTS: PSC was diagnosed in 50 patients in four different tertiary hospitals in Korea. Of them, 18 patients (36.0%) had UC-PSC and 32 patients (64.0%) had PSC alone. The median age at PSC diagnosis was younger in the UC-PSC group than that in the PSC alone group (37 vs. 54 years, P = 0.002). In multivariate analysis, older age at PSC diagnosis (P = 0.007; odds ratio [OR], 0.884; 95% confidence interval [CI], 0.808-0.966) and current smoking habit (P = 0.033; OR, 0.026; 95% CI, 0.001-0.748) were determined to be independent factors for reducing the possibility of developing concomitant UC after PSC. Additionally, UC-PSC was shown to be an independent risk factor for the development of colorectal dysplasia (P = 0.044; OR, 10.829; 95% CI, 1.065-110.127). CONCLUSIONS: Our analysis showed that UC-PSC is more likely to be negatively associated with current smoking and older age at the time of PSC diagnosis. Moreover, UC-PSC increased the risk of colorectal dysplasia.

Additive endoscopic resection may be sufficient for patients with a positive lateral margin after endoscopic resection of early gastric cancer.

BACKGROUND AND AIMS: No well-established treatment strategies exist for lateral margin positivity (LM+) alone after endoscopic resection (ER) of early gastric cancer (EGC). Thus, we aimed to clarify a treatment strategy for non-curative resection (non-CR) with LM+ alone after ER in EGC. METHODS: Among 2065 patients with EGC treated by ER, 76 (3.6%) with only LM+ after non-CR of EGC were reviewed retrospectively. Of these, 28 underwent gastrectomy, 25 underwent argon plasma coagulation (APC), and 23 underwent repeat ER (re-ER). We analyzed the clinicopathologic characteristics of all patients and compared those who underwent additive surgery, APC, or re-ER. RESULTS: Of the 76 patients, 28 (36.8%) fulfilled the absolute criteria and 48 (63.2%) the expanded criteria for ER. Among the latter patients, the proportion undergoing additive surgery was 75.0%, higher than that of patients in the former group (P = .014). Residual cancer cells were observed in 70.6% of patients after additive surgery or re-ER. Residual cancer cells were observed significantly more often in patients with undifferentiated-type than in those with differentiated-type EGC (P = .02). However, no lymph node metastasis was observed in any patient after additive surgery. CONCLUSIONS: Our results suggest that endoscopic treatment may be a sufficient additive therapy for patients with LM+ alone after ER, irrespective of whether the absolute or expanded ER criteria are used. However, as complete ablation of remnant cells cannot be guaranteed, re-ER is a better additive treatment than APC.

A simple scoring model for advanced colorectal neoplasm in asymptomatic subjects aged 40-49 years.

BACKGROUND: Limited data are available for advanced colorectal neoplasm in asymptomatic individuals aged 40-49 years. We aimed to identify risk factors and develop a simple prediction model for advanced colorectal neoplasm in these persons. METHODS: Clinical data were collected on 2781 asymptomatic subjects aged 40-49 years who underwent colonoscopy for routine health examination. Subjects were randomly allocated to a development or validation set. Logistic regression analysis was used to determine predictors of advanced colorectal neoplasm. RESULTS: The prevalence of overall and advanced colorectal neoplasm was 20.2 and 2.5% respectively. Older age (45-49 years), male sex, positive serology of Helicobacter pylori, and high triglyceride and low high-density lipoprotein (HDL) levels were independently associated with an increased risk of advanced colorectal neoplasm. BMI (body mass index) was not significant in multivariable analysis. We developed a simple scoring model for advanced colorectal neoplasm (range 0-9). A cutoff of ≥4 defined 43% of subjects as high risk for advanced colorectal neoplasm (sensitivity, 79%; specificity, 58%; area under the receiver operating curve = 0.72) in the validation datasets. CONCLUSION: Older age (45-49 years), male sex, positive serology of H. pylori, high triglyceride level, and low HDL level were identified as independent risk factors for advanced colorectal neoplasm.

Do surveillance intervals in patients with more than five adenomas at index colonoscopy be shorter than those in patients with three to four adenomas? A Korean Association for the Study of Intestinal Disease study.

BACKGROUND AND AIM: There is controversy about the surveillance interval after colonoscopy when 5-10 adenomas have been found on index colonoscopy. This study aimed to investigate the risk of colorectal neoplasm (CRN) according to the number of adenomas at index colonoscopy. METHODS: A retrospective, multicenter study was conducted at 10 university hospitals in Korea. We included 1394 patients with ≥ 3 adenomas at index colonoscopy. The risk of advanced CRN was compared according to the number of adenomas (intermediate risk group, 3-4 small adenomas or at least one ≥ 10 mm, and high risk group, ≥ 5 small adenomas or ≥ 3 at least one ≥ 10 mm). RESULTS: Overall, 164 (11.8%) developed an advanced CRN after a mean of 4.0 years from baseline colonoscopy. The 3-year and 5-year risk of advanced CRN was 2.1% (95% CI 2.09-2.11) and 14.4% (95% CI 14.36-14.44) in intermediate risk group and 3.2% (95% CI 3.19-3.21) and 23.3% (95% CI 19.15-19.25) in high risk group (P = 0.01). Having ≥ 5 adenomas (OR = 1.57, 95% CI 1.11-2.23, P = 0.01) detected at index colonoscopy was a significant risk factor for developing advanced CRN. CONCLUSIONS: Although risk of advanced CRN in patients with 5-10 adenomas was significantly higher than that in patients with 3-4 adenomas, the cumulative risk at 3 years was low at 3.2%. Thus, we suggest that a 3-year surveillance interval might be appropriate for the patients with 5-10 adenomas, and further prospective studies are needed to investigate whether more intensive surveillance is needed in this group.