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

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

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

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

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

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

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

Background and Aim We aimed to investigate the ability of fluoro-2-deoxy- d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) to detect synchronous neoplasms, specifically obstructive colorectal cancer (CRC) and CRC in the proximal colon and to suggest a management strategy based on FDG PET/CT findings. Methods From the CRC surgery database of our institution, 518 patients with obstructive CRC whose proximal colon could not be examined by colonoscopy and who underwent preoperative FDG PET/CT were eligible for this study. Of these, final analyses were performed in 345 patients who had reference standards for the proximal colon, which were a surgical colectomy specimen and/or postsurgical colonoscopy. The per-patient and per-lesion performances of FDG PET/CT for synchronous CRC diagnosis were determined. Results Of 345 patients, 14 (4.1%) had 14 proximal synchronous CRCs. Thirty-four patients showed 39 areas of abnormal FDG uptake on PET/CT in the colon proximal to the obstructive CRC. PET/CT detected all of the 14 proximal synchronous CRCs. The per-patient PET/CT sensitivity, specificity, positive predictive value, and negative predictive value for proximal synchronous CRC were 100%, 93.9%, 41.2%, and 100%, respectively. Per-lesion values were 100%, 92.6%, 35.9%, and 100%, respectively. The per-lesion sensitivity and negative predictive value of PET/CT for advanced adenoma were 45.5% and 92.7%, respectively. Conclusions The FDG PET/CT shows a high sensitivity and negative predictive value for the detection of proximal synchronous CRC in patients with obstructive CRC, enabling negative findings in the proximal colon on PET/CT to definitively exclude proximal synchronous CRC. Preoperative PET/CT recommended to determine the proper surgical plan in patients with obstructive CRC. [ABSTRACT FROM AUTHOR]

Western-style diet (WD) and dysbiosis are known to be associated with colonic inflammation, which contributes to carcinogenesis. Metformin (Met) exerts anti-inflammatory effects to induce AMP-activated protein kinase (AMPK), resulting in suppressed protein synthesis and reduced cell proliferation. Probiotic VSL#3 (V) modifies microbial composition. We investigated the chemopreventive mechanisms of Met and V in WD-induced colitis-associated colon carcinogenesis. Male BALB/c mice were randomly divided into five groups: a control diet (CD) group, WD group, WD+ Met (250 mg/kg/day) group, WD+V (1.3 million bacteria/day) group, and WD+Met+V group. All mice were exposed to azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) for 7 days. Using HCT-116 human colon cancer cell line, expression of AMPK, extracellular signal-regulated kinase ( ERK), cyclin D1, and Bcl-2 was investigated and cell cycle arrest was assessed. WD enhanced the severity of colitis and tumor growth compared with CD. The combination of Met and V significantly ameliorated colitis and tumor growth by inhibiting macrophage infiltration and maintaining epithelial integrity. In vitro assays showed that the combination therapy promoted late apoptosis by inhibiting cyclin D1 and Bcl-2 and activating pro-apoptotic ERK. A combination therapy with Met and V attenuates tumor growth in a mouse model of WD-induced colitic cancer, suggesting that this strategy could be useful for the chemoprevention of colon cancer. [ABSTRACT FROM AUTHOR]

Background and Aim Current guidelines recommend colon cancer screening for persons aged over 50 years. However, there are few data on colorectal cancer screening in 40- to 49-year-olds. This study assessed the prevalence and risk factors of colorectal neoplasms in 40- to 49-year-old Koreans. Methods We analyzed the results of screening colonoscopies of 6680 persons 40-59 years of age (2206 aged 40-49 and 4474 aged 50-59 years). Results The prevalence of overall and advanced neoplasms in the 40- to 49-year age group was lower than in the 50- to 59-year age group (26.7% and 2.4% vs 37.8% and 3.5%, respectively). However, the prevalence of overall and advanced neoplasms increased to 39.1% and 5.4%, respectively, in 45- to 49-year-old individuals with metabolic syndrome. In the 40- to 49-year age group, age, current smoking, and metabolic syndrome were associated with an increased risk of advanced neoplasms (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.30; OR 3.12, 95% CI 1.20-8.12; and OR 2.00, 95% CI 1.09-3.67, respectively). Conclusions Individuals aged 40-49 years had a lower prevalence of colorectal neoplasms than those aged 50-59 years, but some 40- to 49-year-olds showed a similar prevalence to those aged 50-59 years. Age, current smoking habits, and metabolic syndrome are associated with an increased risk of advanced neoplasms in subjects aged 40-49 years. Further studies are needed to stratify the risks of colon cancer and guide targeted screening in persons younger than 50 years old. [ABSTRACT FROM AUTHOR]

Background: The recurrence rate after standard cold forceps polypectomy (CFP) of diminutive polyps of ≤5 mm has not been fully determined. The aim of this study was to analyze the long-term follow-up results and recurrence rate after CFP of diminutive polyps.Methods: We retrospectively reviewed the medical records of 884 (738 men; age 53 years) asymptomatic subjects who underwent surveillance colonoscopy after CFP of 1-2 diminutive adenomatous polyps. Cumulative recurrence at the CFP site and risk factors for recurrence were analyzed.Results: Overall recurrence over 59.7 months was 17 % after CFP of 1111 diminutive polyps. The rate of definite recurrence was 4 %, and probable recurrence was 13 %. Recurrence as advanced adenoma was 0.5 % (5/1111). The cumulative probabilities of recurrence at 3, 5, and 7 years after CFP were 10.0, 16.0, and 21.1 %, respectively. Multivariate analysis revealed that polyp 4-5 mm in size and right colonic polyp were risk factors for recurrence (hazard ratio [HR] 1.37; 95 % confidence interval [CI] 1.01-1.86 and HR 1.49; 95 % CI 1.08-2.04, respectively). The recurrence rate for 10 endoscopists who performed at least 50 CFPs ranged from 11.0 to 25.2 %; the probability of recurrence in those in the top half in terms of recurrence rate was 1.6-fold higher than that of those in the bottom half (95 % CI 1.17-2.19).Conclusions: Although recurrence may develop after standard CFP of diminutive polyps, recurrence as advanced adenoma is rare. Large polyp size, right colon polyp, and endoscopist are risk factors for recurrence after standard CFP. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aimed to develop and validate a risk score model to estimate the probability of a metachronous advanced colorectal neoplasm (ACRN) at surveillance colonoscopy.Methods: A retrospective analysis of a prospectively obtained database of 11,042 asymptomatic subjects who underwent surveillance colonoscopy after a screening colonoscopy was conducted. Subjects were randomly divided into derivation (n = 7730) and validation sets (n = 3312). From the derivation cohort, risk factors for a metachronous ACRN were identified by a multivariable analysis. Risk points were allocated to each risk factor based on the hazard ratio to develop the Metachronous Advanced colorectal neoplasm Prediction Scoring (MAPS) model, the performance of which was assessed in the validation cohort.Results: In the derivation cohort, age, male, sessile serrated adenoma/polyp, and a high-risk CRN (ACRN or ≥3 adenomas) at screening colonoscopy were independent risk factors for a metachronous ACRN. These variables were incorporated into the MAPS model, and the risk score ranged 0-17 (high MAPS risk arbitrarily defined as 10-17). At the 3-year surveillance colonoscopy, ACRN was found in 5.1 % of the high MAPS risk group versus 3.9 % of the high-risk CRN group. The colonoscopy number needed to detect one metachronous ACRN at the 3-year surveillance was 19.5 (95 % CI 11.7-33.2) for the high MAPS risk group versus 25.8 (95 % CI 15.4-44.0) for the high-risk CRN group. These findings were similarly confirmed in the validation cohort.Conclusions: Our MAPS model based on clinical and colonoscopic parameters effectively predicts the risk of a metachronous ACRN. [ABSTRACT FROM AUTHOR]

Background and Aim Recent studies suggest that the anti-inflammatory agent balsalazide (BSZ) and probiotic agent VSL#3 have potential therapeutic benefits for the treatment of patients with inflammatory bowel disease. However, their effectiveness in preventing colitis-associated carcinogenesis (CAC) remains uncertain. The aim of the present study was to determine the chemopreventive effects of BSZ and VSL#3 in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Methods C57B/L6J mice were randomly divided into four groups: CAC group, BSZ group, VSL#3 group, and BSZ + VSL#3 group. After 2 weeks, the AOM/DSS model was induced by AOM injection followed by two cycles of 2% DSS. Results During first and second cycles of DSS, the number of F4/80-positive macrophages was significantly lower in the drug-treated groups compared with the CAC group ( P < 0.05). At the endpoint, the total numbers of tumors in the drug-treated groups were significantly low compared with the CAC group ( P < 0.05), and the drug-treated groups had significantly lower F4/80-positive macrophages in the tumor stroma ( P < 0.01). The protein production of macrophage inflammatory protein 1 beta, monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-10 in the colon tissues decreased in concordance with the plasma concentrations of the cytokines ( P < 0.05). The drug-treated groups revealed lower expression of p-STAT3 compared with the CAC group. In addition, BCL2 decreased, and BAX increased markedly in the BSZ + VSL#3 group. Conclusions These results revealed that BSZ and VSL#3 have chemopreventive effects against CAC through IL-6/STAT3 suppression. BSZ and VSL#3 could be suitable options for chemoprevention of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background and Aim It is generally assumed that gastric cancer (GC) in young patients has different clinicopathologic characteristics than that of elderly patients. Although recurrence is an important factor in determining prognosis, traditional clinicopathological factors are sometimes inadequate for predicting recurrence in individuals. Therefore, we aimed to identify miRNAs with the potential to predict recurrence in young patients. Methods Young patients (age <40 years) undergoing gastrectomy for potentially curable GC (stage III) at Asan Medical Center participated in this study. A total of 50 GC patients with ( n = 28) and without ( n = 22) GC recurrence were selected for analysis. miRNA microarrays were analyzed to screen tissue samples ( n = 7), and we validated the selected miRNAs by quantitative PCR in validation samples ( n = 43). Results Two miRNAs (hsa-miR-21-5p and hsa-miR-451a) identified in the microarray analysis were evaluated in the validation samples. Among the validation samples containing intratumoral stroma ≥ 70 ( n = 35), hsa-miR-21-5p was more highly expressed in the recurrence group than in the nonrecurrence group (fold change 1.82, P = 0.03). In the validation samples with intratumoral stroma ≥ 70, the ΔCt of hsa-miR-21-5p, which was >3.35, had a sensitivity and specificity of 86.7% and 65.5%, respectively, for predicting recurrence, with an area under the ROC curve of 0.723. Conclusions miR-21-5p may be useful as a predictor of recurrence in young GC patients whose tumors contain a high proportion of intratumoral stroma. The combination of this miRNA with conventional clinicopathological factors should allow patient prognoses to be more accurately predicted. [ABSTRACT FROM AUTHOR]

Background and Aim: Although metabolic factors such as obesity and hyperlipidemia were reported to be associated with high prevalence of colorectal neoplasm (CRN), their influence on the occurrence of CRN at surveillance colonoscopy has not been clarified. The purpose of this study was to analyze the association between metabolic factors and the risk of CRN at the time of surveillance colonoscopy. Methods: We reviewed the medical records of 1792 asymptomatic subjects (average 52.1 years, 1233 male) who underwent screening and follow-up surveillance colonoscopies. Fasting glucose level, fasting insulin level, hemoglobin A1c (HbA1c), lipid profile, high sensitivity C-reactive protein, and colonoscopic findings at the time of baseline screening were analyzed to find any associations with the occurrence of CRN at the time of surveillance colonoscopy. Results: The median interval between screening and surveillance colonoscopies was 3.34 years. The 3- and 5-year cumulative CRN incidences were 22.3% and 54.8%, respectively. Several metabolic factors such as hypertension, waist circumference, fasting insulin, fasting glucose, HbA1c, and triglyceride were associated with the occurrence of CRN in univariate analysis. Age, current alcohol drinker status, and high-risk colonoscopy findings at baseline remained independent risk factors for CRN occurrence in multivariate analysis. High waist circumference was also an independent risk factor (hazard ratio 1.03, 95% CI 1.02-1.04; P < 0.001). Conclusions: Metabolic factors, especially waist circumference, affect CRN occurrence at the time of surveillance colonoscopy. The surveillance colonoscopy interval may be optimized based on metabolic factors and screening colonoscopy findings. [ABSTRACT FROM AUTHOR]

Background and Aims: To date, no large-scale studies have evaluated long-term outcomes of infliximab (IFX) treatment in Korean patients with Crohn's disease (CD).Methods: We analyzed long-term clinical responses to IFX in 582 Korean CD patients who received scheduled IFX treatments at Asan Medical Center. Clinical responses were defined as maintaining IFX without major abdominal surgery (MAS) or dose intensification.Results: Between February 2002 and July 2015, a total of 11,990 IFX infusions were administered to 582 Korean patients with CD over a median period of 36 months. At the end of follow-up, 316 (54.3 %) were still receiving IFX without MAS (71 patients, 12.2 %) or dose intensification (86 patients, 14.8 %). IFX was stopped in 109 (18.7 %) patients because of a loss of response (48 patients, 8.2 %), adverse events (30 patients, 5.2 %), or patient preferences or problems with reimbursement (31 patients, 5.3 %). The cumulative survival for maintenance of IFX without MAS or dose intensification was 89.0, 75.9, 68.3, and 50.8 % at 1, 2, 3, and 5 years, respectively. Multivariate regression analysis identified older age at the initiation of IFX (≥40 years, P = 0.006) and a longer disease duration (≥3 years, P = 0.020) as independent positive predictors of a poorer response to IFX.Conclusions: The long-term efficacy of IFX in a large, real-life cohort of Korean patients with CD appears to be similar to that in previously published Western studies. Our findings support the early use of IFX to obtain better clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Few studies have been conducted on the progression of mild Crohn's disease (CD). We aimed to investigate the natural course in mild CD patients with or without bowel damage, to identify predictors of bowel resection and to calculate the requirement for rescue medication. Methods: A total of 104 patients with mild activity (150 < CDAI < 220) with or without bowel damage were identified from among 1050 CD patients between January 2008 and May 2014. Univariate and multivariate analysis was used to identify factors associated with bowel resection. The cumulative probabilities of bowel resection and rescue medication such as steroids or anti-TNF agents were calculated. Results: The median follow-up duration was 28.2 months (IQR 26.7). Cumulative probabilities of bowel resection were 0.2, 11.8 and 42.4 % at 1, 3 and 5 years respectively. The CD patients with bowel damage had a higher bowel resection rate than those without bowel damage ( P < 0.001). The cumulative probabilities of corticosteroid-requirement were 3.0, 19.6 and 78.4 % of patients at 1, 3 and 5 years, respectively, and 2.1, 11.9 and 56.1 %, in terms of the cumulative probabilities of requiring anti-TNF agents. Patients with elevated CRP (>1.6 mg/dL) were more likely to undergo bowel resection ( P = 0.032). Conclusions: Even in CD patients with mild disease activity, the cumulative probability of bowel resection is not low if they have bowel damage or elevated CRP at baseline. Mild CD patients with bowel damage or elevated CRP at baseline need special attention. [ABSTRACT FROM AUTHOR]

Background and Aims: The therapeutic outcome of endoscopic submucosal dissection (ESD) for large protruding tumors has not yet been evaluated. We aimed to compare the outcomes of ESD in protruding tumors with those of laterally spreading tumors (LSTs).Methods: Endoscopic submucosal dissection was attempted in 218 patients with 220 colorectal tumors ≥30 mm in diameter (67, protruding tumors; 153, LSTs) from July 2007 to June 2014. We retrospectively reviewed patient medical records, therapeutic outcomes, and procedure-related adverse events. This study defined lesions with a height of 10 mm or more as protruding tumors and those with a height under 10 mm as LSTs.Results: The mean lesion diameter, height, and volume were 43.8, 9.5 mm, and 13.6 cm(3), respectively. The mean procedure time was 75.5 min. Deep submucosal cancer was more frequent in protruding tumors than in LSTs (11.9 vs. 2.6%, P = 0.005). Severe fibrosis was more common in protruding tumors than in LSTs (19.4 vs. 3.9%, P < 0.001). En bloc resection and complete resection rates were lower in protruding tumors than in LSTs (en bloc resection, 76.1 vs. 92.8%, P = 0.001; complete resection, 64.2 vs. 79.1%, P = 0.020). Intra- and post-procedural bleeding were more frequent in protruding tumors than in LSTs (22.4 vs. 2.6%, P < 0.001; 6.0 vs. 0.7%, P = 0.031, respectively). By multivariate analysis, protruding tumor morphology (odds ratio 1.919, P = 0.048) and tumor size ≥60 mm (odds ratio 2.490, P = 0.030) were associated with incomplete resection.Conclusions: Endoscopic submucosal dissection for protruding tumors is less effective than ESD for LSTs, with lower rate of complete resection occurring with protruding tumors. [ABSTRACT FROM AUTHOR]

Background: Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals.Objectives: We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD.Methods: We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity.Results: No difference was seen in the enteric α-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P < 0.05). No significant correlation was found between the presence of alpha-synuclein immunoreactivity and the motor and nonmotor features of PD.Conclusions: The presence of alpha-synuclein immunoreactivity in gastric and colonic mucosa was detected in a similar manner in patients with PD, patients with MSA, and controls, thus suggesting a limited role of enteric mucosal alpha-synuclein as a diagnostic biomarker for PD. Future studies are warranted to detect pathological alpha-synuclein strains. [ABSTRACT FROM AUTHOR]

Background: Experience in gastric endoscopic submucosal dissection (ESD) has been suggested as a prerequisite for performing colorectal ESD by some experts.Aims: To evaluate the feasibility of performing colorectal ESD without experience in gastric ESD.Methods: Between November 2009 and December 2013, ESD was attempted for 250 colorectal lesions by an endoscopist having extensive colonoscopy experience but no prior experience of gastric ESD. All attempts were categorized according to the chronological order of procedures: group 1, attempts 1-50; group 2, attempts 51-100; group 3, attempts 101-150; group 4, attempts 151-200; and group 5, attempts 201-250. Procedure-related outcomes were analyzed.Results: En bloc resection rate ≥80% was achieved after initial ten ESD attempts. The ESD success rate (72, 80, 90, 90, and 94% in group 1-5, respectively; p for trend = 0.001), perforation rate (14, 14, 6, 6, and 0% in group 1-5, respectively; p for trend = 0.003), and macroperforation rate (6, 6, 2, 2, and 0% in group 1-5, respectively; p for trend = 0.042) improved as experience accumulated. Performing >100 ESDs, rectal location, and absence of submucosal fibrosis were independent predictors of successful procedure.Conclusion: Colorectal ESD can be safely and effectively performed by an endoscopist having extensive experience in colonoscopy-related procedures even without previous experience of gastric ESD. Meticulous case selection for ESD novice and active supervision by expert endoscopists during the initial learning period may minimize the risk of perforation. [ABSTRACT FROM AUTHOR]

Background: The role of postoperative radiation therapy (RT) after local excision (LE) of deep submucosal invasive rectal cancer remains unclear. We evaluated the efficacy of adjuvant RT after LE of early rectal cancer with deep submucosal invasion.Methods: We screened 227 patients who underwent transanal excision or endoscopic removal of deep submucosal invasive rectal cancer between 1992 and 2012, of which 66 did not undergo radical surgery owing to the patient's preference or poor medical conditions. Of these, 35 (53 %) underwent LE alone (LE group) and 31 (47 %) received adjuvant RT after LE (LE + RT group). Nine patients in the RT group received concurrent adjuvant chemotherapy with 5-fluorouracil. Two independent pathologists reviewed histological data.Results: The mean age of patients in the LE + RT and LE groups was 59.5 ± 9.6 and 55.3 ± 11.2 years, respectively. The mean follow-up duration was 78.7 ± 66.7 months in the LE + RT group and 70.5 ± 45.7 months in the LE group. Cancer eventually recurred in six patients (9.1 %; two in the LE + RT group and four in the LE group). In five of these patients, recurrence occurred within 4 years after the initial treatment. The other patient, who was in the LE group, exhibited multiple lymph node metastases at the 116-month follow-up. Kaplan-Meier estimates of recurrence-free survival at 5 years after treatment were 96.8 % in the LE + RT group and 97 % in the LE group (P = 0.657).Conclusion: RT after LE of early rectal cancer with deep submucosal invasion might not improve recurrence-free survival compared with LE alone. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the optimal cut-off of the maximum standard uptake value (SUVmax) for the detection of colorectal neoplasms and to suggest those for whom further colonoscopy is recommended among patients with incidental colonic uptake on positron emission tomography-computed tomography (PET-CT). Materials and methods. In 306 patients who underwent colonoscopy within 3 months of receiving PET-CT between January and December 2009, measurements of the per-patient and per-lesion diagnostic performance of PET-CT for the detection of colonic neoplasms were obtained. Receiver operating characteristic (ROC) analysis was used to identify the SUVmax that provided a high probability of diagnosing malignancy and high-grade dysplasia. Results. The per-patient and per-lesion PET-CT detection sensitivities for malignancies were 93.3% (28/30; 95% confidence interval (CI) 76.5% to 98.9%) and 93.5% (29/31, 95% CI 77.2% to 98.9%), respectively; the sensitivities for high-grade dysplasia were both 90.0% (9/10; 95% CI 54.1% to 99.5%). As a criterion to specifically detect both malignancy and high-grade dysplasia on focal uptake, a SUVmax greater than 2.5 yielded a 92.3% per-lesion sensitivity and a 42.9% per-lesion positive predictive value (PPV). In the ROC curve analysis, a cut-off value of SUVmax = 5.8 was established, at which the sensitivity, PPV and positive likelihood ratio for diagnosing malignancy and high-grade dysplasia were 71.8% (28/39; 95% CI 54.9% to 84.5%), 84.8% (28/33; 95% CI 67.3% to 94.3%) and 6.9, respectively. Conclusion. The optimal cut-off value to identify a malignancy or high-grade dysplasia was SUVmax = 5.8. However, to avoid missing a malignancy or high-grade dysplasia, a colonoscopy should be performed above a SUVmax = 2.5. [ABSTRACT FROM AUTHOR]

Objectives:Digital rectal examination (DRE) is a simple clinical method to diagnose anorectal disorders. High-resolution antorectal manometry (HRAM) based on a spatiotemporal plot is expected to promote improved diagnostic accuracy. However, there are no reports comparing the effectiveness of DRE and HRAM. The aim of our study was therefore to evaluate the diagnostic value of DRE compared with HRAM.Methods:A total of 309 consecutive patients with chronic constipation (n=268) or fecal incontinence (n=41) who underwent a standardized DRE, HRAM, and balloon expulsion test were enrolled in this study. The diagnostic yield of DRE compared with HRAM was determined, and agreement between DRE and HRAM data was evaluated.Results:Of the constipated patients, 207 (77.2%) were diagnosed with dyssynergia using HRAM. The sensitivity, specificity, and positive predictive value of DRE in the diagnosis of dyssynergia were 93.2%, 58.7%, and 91.0%, respectively, and moderate agreement was seen between the two modalities (κ-coefficient =0.542, P<0.001). In patients with fecal incontinence, there was moderate agreement in terms of anal squeeze pressure between the two modalities (κ-coefficient =0.418, P=0.006); however, there was poor agreement for anal resting tone (κ-coefficient =0.079, P=0.368).Conclusions:DRE shows high sensitivity and positive predictive value in detecting dyssynergia compared with HRAM, and could therefore be used as a bedside screening test for the diagnosis of this disorder. Further studies are warranted to evaluate the correlation between DRE and HRAM in assessing anal sphincter pressure. [ABSTRACT FROM AUTHOR]

Goals. The purpose of this study is to investigate the learning curve for colonoscopic polypectomy (CP) by trainee endoscopists. Background. The amount of training required to achieve technical competence for CP is uncertain. Study. The CP times and en bloc resection rates of three experienced colonoscopists were obtained from 240 procedures. These data were compared to those of three gastroenterology trainees who performed 750 CP procedures. A trainee procedure was deemed to be a success if en bloc resection was obtained and the CP time was within twice the median CP time of the experienced colonoscopists. Trainees were deemed to be technically competent when they achieved a CP success rate of greater than or equal to 80%. Results. The median CP times and en bloc resection rates for the experienced colonoscopists and trainees were 79 s (range, 20-301 s) and 99.6% (239/240), and 118 s (range, 36-1051 s) and 95.6% (717/750), respectively. The trainee success rate of CP was 72% (540/750). The success rate of the procedure was associated with increased trainee experience ( p = 0.003) and reached 80% after 250 procedures. The CP time significantly decreased ( p < 0.001) and en bloc resection rate significantly increased ( p = 0.011) as trainee experience accumulated. The level of experience was an independent predictor for successful CP. Conclusions. The achievement of technical competence with CP was associated with an accumulation of approximately 250 procedures. These findings suggest that dedicated education and training programs for CP are warranted. [ABSTRACT FROM AUTHOR]

Background and Aim Appendectomy protects against the development of ulcerative colitis ( UC). However, the relationship between appendectomy and the clinical course of UC is complex, and could be impacted by a number of variables. The aim of this study was to compare the clinical course of UC between appendectomized patients and nonappendectomized patients in Korea. Methods Data on 2648 UC patients were retrieved from the Inflammatory Bowel Disease registry at Asan Medical Center. This retrospective cohort study compared the clinical course of UC in 68 patients who received an appendectomy before their UC diagnosis and 2544 patients who did not receive this procedure. A nested case-control study was also conducted to compare the disease course before and after appendectomy in 36 patients who received this surgery after UC diagnosis. To control for potential confounders, 144 matched controls were retrieved from among 2544 nonappendectomized patients Results In the retrospective cohort study, an appendectomy before UC diagnosis demonstrated no influence on disease extent at diagnosis, rates of medication use, proximal disease extension, or colectomy. The 10- and 20-year probabilities of receiving a colectomy were 12.7% and 20.6%, respectively, in appendectomized patients, in comparison with 8.9% and 16.4%, respectively, in nonappendectomized patients ( P = 0.81). According to the nested case-control study, an appendectomy after UC diagnosis did not change the subsequent disease course in terms of medication use, proximal disease extension, or hospital admission rate. The adjusted ratio of hospital admissions after appendectomy versus before appendectomy was 1.01 (95% confidence interval = 0.46-2.23; P = 0.97). Conclusions Appendectomies performed before or after UC diagnosis do not affect its clinical course in the Korean population. [ABSTRACT FROM AUTHOR]

Objective. Limited data are available on the incidence and risk factors of colorectal cancer (CRC) in Asian patients with inflammatory bowel disease (IBD). Material and methods. Information on 5212 Korean patients with IBD (2414 with Crohn's disease [CD] and 2798 with ulcerative colitis [UC]) was retrieved from the IBD registry of Asan Medical Center. Data on CRC incidence for the entire Korean population were derived from the Korean Statistical Information Service. Results. During 39,951 person-years of follow-up (17,679 for CD and 22,272 for UC), 30 patients (12 with CD and 18 with UC) developed CRC. The standardized incidence ratio (SIR) of CRC was 6.0 (95% confidence interval [CI], 3.10-10.48) for CD and 1.68 (95% CI, 1.00-2.66) for UC; it was 9.69 (95% CI, 5.01-16.93) for CD with colonic involvement and 4.31 (95% CI, 2.46-7.00) for extensive UC. The SIR was also increased in patients diagnosed with IBD at younger than 30 years old. CRC location was the low rectum in 11 of 12 CD patients (91.7%). The cumulative probability of rectal cancer was higher in CD patients with a perianal fistula than in those without a perianal fistula ( p = 0.02). Conclusions. A high prevalence of perianal fistulas in Korean CD patients may be the cause of the predominance of low rectal cancer in this population and the higher SIR of CRC in Koreans than in Westerners. In contrast, the SIR of CRC in Korean UC patients may be similar to that in Western UC patients. [ABSTRACT FROM AUTHOR]

Background: Current guidelines for the surveillance colonoscopy interval are largely based on the most recent colonoscopy findings. Aim: We aimed to evaluate differences in the probability of high-risk neoplasm recurrence according to the two previous colonoscopy findings. Methods: This was a retrospective cohort study from a tertiary-care center. A total of 4,143 subjects who underwent three or more colonoscopies for screening or surveillance purposes from January 2001 to December 2011 were enrolled. We compared the probability of high-risk neoplasm detection on follow-up colonoscopies after the second colonoscopy based on risk categories in both the second and first colonoscopies. Results: At the final colonoscopy, 370 participants (8.9 %) had high-risk neoplasms. In patients with a normal second colonoscopy, the probability of high-risk neoplasm recurrence was different between those with normal, low-risk, and high-risk findings at the first colonoscopy (3.8, 6.8, and 17.7 %, respectively). The hazard ratio of a high-risk neoplasm at the final colonoscopy for patients with a normal second and low-risk first colonoscopy over a normal second and normal first colonoscopy was 3.07 (95 % CI 2.04-4.64, P < 0.001). The hazard ratio of high-risk neoplasm at the final colonoscopy for patients with a normal second and high-risk first colonoscopy over a normal second with normal first colonoscopy was 7.88 (95 % CI 4.90-12.67, P < 0.001). Conclusions: The rate of high-risk colorectal neoplasm recurrence differs according to the two previous colonoscopy findings. Therefore, surveillance intervals could be adjusted not just only by the most recent colonoscopy findings but also by considering two previous colonoscopy findings. [ABSTRACT FROM AUTHOR]

Background: The optimal colon-cleansing method after failure of bowel preparation (BP) for colonoscopy has not been established. Aims: We aimed to compare BP rescue methods after failed initial BP and to identify risk factors for rescue BP failure. Methods: Eighty-five patients with BP failure after 4 L polyethylene glycol (PEG) ingestion were prospectively enrolled from March 2008 to March 2012. A second colonoscopy was performed either on the same day after ingestion of another 2 L PEG (group A) or 1 week later after ingestion of 4 L PEG plus 20 mg oral bisacodyl (group B). Differences between groups in terms of BP quality and risk factors for a poor BP on the second colonoscopy were investigated. Results: Median patient age was 59 years, 45 were male (52.9 %), and 17 (20 %) had poor BP on the second colonoscopy. For group B, the multivariable-adjusted odds ratio (OR) for poor BP on the second colonoscopy relative to group A was 0.68 (95 % confidence interval [CI], 0.16-2.95). Adequately ingested PEG during the initial colonoscopy was associated with poor BP on the second colonoscopy (OR 4.05; 95 % CI 1.04-15.75). The two groups had similar patient discomfort rates during the second BP. Conclusions: The two groups did not differ in rescue BP failure rate. Initial BP failure after adequate consumption of 4 L PEG may be a risk factor for rescue BP failure. A stricter BP regimen should be considered for these patients. [ABSTRACT FROM AUTHOR]

Objective. Few data are available on the influence of a colonoscope length for trainees, which could affect both the duration of training and colonoscopy quality. We conducted this study to validate which scope needs more duration for training to reach technical competence and to shows better quality indicators during diagnostic colonoscopy. Materials and methods. We conducted a prospective randomly assigned study from April 2010 to February 2011 at Asan Medical Center. Among the 1329 patients enrolled, 1200 colonoscopies were analyzed. We compared cecal intubation rate, adenoma detection rate, cecal intubation time (<20 min), and withdrawal time between the trainees using the intermediate-length colonoscope and those using long-length colonoscope. Results. Trainees who used the long-length colonoscope showed a higher overall cecal intubation rate (88.2% vs. 81.0%, p = 0.001) and adenoma detection rate (49.7% vs. 34.2%, p < 0.001) than those using the intermediate-length colonoscope. The successful cecal intubation rate improved significantly and reached the requisite standard of competence (>90%) after 90 procedures in the long-length colonoscope group. However, the trainees using the intermediate-length colonoscope reached the requisite standard of competence after 150 procedures. Logistic regression analysis revealed that prolonged cecal intubation was associated with the use of the intermediate-length colonoscope, poor colon preparation, a small number of esophagastroduodenoscopy or sigmoidoscopy procedures conducted, and pain during procedures. Conclusions. During the same training period, use of the long-length colonoscope in trainee was better in terms of reaching competency and quality indicators, and was less painful for the patients during colonoscopic procedures. [ABSTRACT FROM AUTHOR]

A mitochondria-targeting ratiometric probe was designed for γ-glutamyltranspeptidase (γGT). Mechanistic study by HPLC and an inhibitor assay showed that the probe underwent γGT-mediated amide-to-amine transformation and induced a ratiometric fluorescence response in cellular mitochondria. Further application was successful for the detection of cancerous colons in mice. [ABSTRACT FROM AUTHOR]

Background Anorectal manometry with simulated evacuation ( SE) has limited applicability in predicting balloon expulsion ( BE) test results. The newly developed high-resolution anorectal manometry ( HRAM) technique can yield spatiotemporal plots with three-dimensional pressurization. We aimed to define new parameters based on three-dimensional integrated pressurized volume ( IPV) for predicting the BE test results in asymptomatic normal individuals. Methods Fifty-four asymptomatic healthy individuals were prospectively enrolled. BE tests were performed using 50 mL of water, and a requirement of more than 1 min was considered as delayed BE. HRAM profiles were converted into ASCII files and analyzed using a MATLAB program. A three-dimensional IPV was plotted after transforming the data to a cubic spline interpolation followed by resampling the manometry position at 0.1-cm intervals. Key Results Eight of the 54 (15%) individuals demonstrated delayed BE. Conventional manometric profiles did not differ significantly between cases of early and delayed BE. Receiver-operator characteristic curve analysis revealed that the ratio of the IPVs of the upper 1 cm to the lower 4 cm of the anorectal canal with balloon distension was more predictable of the BE results (area under curve, 0.73: 95% confidence interval, 0.53-0.92; p = 0.04) than the other IPVs or their ratios. Conclusions & Inferences The newly developed IPV methods could predict delayed BE tests during SE better than the conventional parameters defined on the basis of linear waves. Well-designed prospective trials on a large number of subjects are warranted to validate the clinical application of this novel parameter. [ABSTRACT FROM AUTHOR]

Background and Aim Little is known about the clinicopathological characteristics of primary gastrointestinal T-cell lymphomas ( PGITL). This study evaluated the clinical and endoscopic features of the pathological subtypes of PGITL. Methods Forty-two lesions in 36 patients with PGITL were assessed, including 15 enteropathy-associated T-cell lymphomas ( EATL), 13 peripheral T-cell lymphomas ( PTCL), 10 NK/ T-cell lymphomas ( NK/ TL), and four anaplastic large cell lymphomas ( ALCL). Results PTCL occurred more frequently in the stomach and duodenum and NK/ TL more frequently in the small and large intestines ( P = 0.009). The endoscopic features of the four subtypes were similar ( P = 0.124). Fifteen of 41 lesions (36.6%) were Epstein- Barr virus ( EBV) positive, with NK/ TL more likely to be EBV positive than the other types ( P < 0.001). First endoscopy and first computed tomography ( CT) scan indicated that 65.4% and 51.4% of the lesions, respectively, were malignant, and that 43.2% and 42.3%, respectively, were GI lymphomas. The two modalities together correctly diagnosed about half of the lesions before biopsy. Intestinal perforation was associated with small bowel location ( P < 0.001) and infiltrative type ( P = 0.009), and was more common in NK/ TL than in the other subtypes ( P = 0.015). Multivariate analysis showed that higher international prognosis index ( P = 0.008) and the presence of complications ( P = 0.006) were associated with poor prognosis. Survival was poorer in patients with small bowel lesions than with lesions at other locations ( P = 0.048). Conclusions The four main pathological types of PGITL differed in clinical characteristics. As PGITL was often not diagnosed by initial endoscopic or radiological examination, a high index of suspicion is necessary to ensure its early diagnosis. [ABSTRACT FROM AUTHOR]

Background: The impact of one-stage polypectomy (removal of all neoplasms during diagnostic colonoscopy) versus two-stage polypectomy (removal of all neoplasms during therapeutic colonoscopy following the initial diagnostic colonoscopy) on the development of metachronous neoplasms is poorly understood. Our aim was to compare the effects of one- versus two-stage polypectomy on the development of metachronous neoplasms Methods: We retrospectively reviewed the medical records of 249 patients in a tertiary center who underwent one-stage polypectomy, which was followed by one or more surveillance colonoscopy. The development of metachronous neoplasm in this group was compared with that of an age- and sex-matched two-stage polypectomy group consisting of 498 patients Results: In total, 346 (46.3 %) patients developed any metachronous neoplasm and 29 (3.9 %) patients developed advanced metachronous neoplasm. The 5 years cumulative incidences of any and advanced metachronous neoplasm were 46.2 and 5.0 %, respectively, in the one-stage group, which are not significantly different from the rates of 50.7 and 3.3 % in the two-stage group ( p = 0.94 and 0.30, respectively). The only significant risk factor for developing any metachronous neoplasm was ≥3 neoplasms at the baseline polypectomy [hazard ratio (HR) 1.75; 95 % confidence interval (CI) 1.41-2.17; p < 0.001]. The only significant risk factor for developing advanced metachronous neoplasm was advanced neoplasm at the baseline polypectomy (HR 2.37; 95 % CI 1.16-4.84; p = 0.01). One- and two-stage polypectomy did not affect the development rates of metachronous neoplasm Conclusions: The risks of developing metachronous neoplasm may be similar following one- and two-stage polypectomy. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of infliximab in the treatment of patients with ulcerative colitis (UC) in Asia is still unclear. The aim of this study was to evaluate the clinical outcomes of infliximab therapy in Korean UC patients, including efficacy and predictors of response. Methods: Patients who received infliximab induction therapy for moderate to severe UC at Asan Medical Center were retrospectively analyzed. The demographic characteristics of these patients and their clinical outcomes following infliximab therapy were evaluated. Results: Of the 89 UC patients receiving infliximab induction therapy, 53 (59.6 %) were steroid-refractory and 36 (40.4 %) were steroid-dependent. At the initiation of infliximab, the median Mayo score was 9 (range 7–12). After the induction therapy of infliximab, 59 patients (66.3 %) demonstrated a clinical response at week 8, of which 29 (32.6 %) were determined to be in clinical remission. A colectomy was performed within 1 year after infliximab initiation in 11 (36.7 %) of 30 patients who displayed no clinical response to infliximab therapy, but in none of the 59 patients who showed a response to this drug ( p < 0.001). Multivariate regression analysis identified severe disease (Mayo score ≥ 11) at the initiation of infliximab ( p = 0.007) and history of cytomegalovirus colitis within 3 months prior to infliximab treatment ( p = 0.001) as independent positive predictors of nonresponse to infliximab. Conclusions: The efficacy of infliximab in Korean UC patients seems to be similar to that of previously published Western reports. Severe disease and a history of cytomegalovirus colitis are predictors of a nonresponse to infliximab. [ABSTRACT FROM AUTHOR]

Objective. The long-term efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (UC) is still unclear. We aimed to evaluate the efficacy of AZA in patients with steroid-dependent UC. Material and methods. We retrospectively reviewed die medical records of 106 patients with steroid-dependent UC who were administered AZA. Three-year outcomes of AZA therapy were evaluated. The outcome of the treatment was defined as (1) success, indicating induction and maintenance of remission throughout the study period (complete success) or remission followed by infrequent and short relapses (partial success); or (2) failure, indicating the absence of remission, frequent or prolonged relapses, infliximab administration, or colectomy. Results. Of the 106 patients, 73 (68.9%) continued on AZA for >6 months (AZA therapy group) and 33 (31.1%) discontinued AZA within 6 months due to intolerance (AZA intolerance group, n = 20), colectomy (n = 6), or follow-up loss (n = 7). Three-year outcomes for 106 patients were success in 54.7% (complete success, 35.8%; partial success, 18.9%), failure in 32.1% (frequent or prolonged relapses, 12.3%; infliximab administration, 5.6%; colectomy, 14.2%), and follow-up loss or death in 13.2%. The success rate increased to 71.2% (complete success, 46.6%; partial success, 24.7%) when the analysis was confined to the 73 patients who continued AZA for > 6 months. The 3-year success rate was higher in the AZA therapy group (71.2%) than the AZA intolerance group (25.0%) (p < 0.001). Conclusions. AZA is an effective treatment for steroid-dependent UC. The efficacy of AZA is well sustained over 3 years. [ABSTRACT FROM AUTHOR]

Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Background and Aims: 15-Hydroxprostaglandin dehydrogenase (15-PGDH) mediates a colon neoplasia suppressor pathway, acting through metabolic antagonism of cyclooxygenase-mediated colon carcinogenesis. To determine whether the colon tumor prevention activity of 15-PGDH acts as a constant or variable effect among individuals, we determined whether 15-PGDH levels remain stable over subsite and time in the human colon, determined the extent of differences in 15-PGDH levels between different individuals, and determined whether 15-PGDH modulation mediates any part of the anti-colon tumor effect of aspirin. Methods: Using real-time PCR, we measured 15-PGDH mRNA to determine the correlation of 15-PGDH level in replicate colon biopsies, in biopsies from throughout the length of the colon, in repeat biopsies taken 4 months apart, and in paired biopsies of individuals taken before and after aspirin treatment, and by Western-blot for 15-PGDH protein in mice. Results: Colonic 15-PGDH levels varied 4.4-fold across the human population. Within individuals, 15-PGDH levels proved highly reproducible ( r = 0.81 in duplicate biopsies) and stable along the length of the colon, with average 15-PGDH levels deviating by only 17 % from rectum to cecum. An individual's 15-PGDH levels are also highly stable over time, with a median coefficient of variation over a 4-month interval of only 12 %. Last, colonic 15-PGDH levels proved resistant to alteration by aspirin, with only a 10 % difference in 15-PGDH levels measured before and after aspirin treatment. Conclusions: 15-PGDH levels vary across the population in a stable and reproducible manner, and are resistant to alteration by aspirin. 15-PGDH represents an independent target for modulation by candidate colon tumor chemopreventive agents. [ABSTRACT FROM AUTHOR]

Background and Aims Although capsule endoscopy ( CE) is widely used as a first-line diagnostic modality for obscure gastrointestinal bleeding ( OGIB), the rebleeding rate after negative CE varies according to different studies. We tried to elucidate the outcomes after negative CE for OGIB and to determine the risk factors associated with rebleeding. Methods We retrospectively reviewed data from 125 patients who had received CE for OGIB. Results Pill Cam SB capsules were used for 92 patients (73.6%) and SB2 capsules for the other 33 (26.4%). The complete visualization of the small bowel was achieved in 93 patients (74.4%). Of the 63 patients (50.4%) who showed negative CE results, 60 patients did not receive any further specific treatment for OGIB, and were analyzed for the rebleeding rate and risk factors for rebleeding. Of the 60 patients, rebleeding episodes were observed in 16 patients (26.7%), and the cumulative rebleeding rates after 6, 12, 24, and 36 months were 12.4%, 14.3%, 28.7%, and 35.9%, respectively. Substantial rebleeding events were observed with similar frequency both after negative CE without subsequent treatment (26.7%) and after positive CE without specific treatment (21.2%) ( P = 0.496). Conclusions Considerable rebleeding episodes were observed after negative CE result for OGIB. Further complementary diagnostic work-ups and close follow-up are needed to be considered for patients with OGIB and negative CE results. [ABSTRACT FROM AUTHOR]

Chronic constipation (CC) may impact on quality of life. There is substantial patient dissatisfaction; possible reasons are failure to recognize underlying constipation, inappropriate dietary advice and inadequate treatment. The aim of these practical guidelines intended for primary care physicians, and which are based on Asian perspectives, is to provide an approach to CC that is relevant to the existing health-care infrastructure. Physicians should not rely on infrequent bowel movements to diagnose CC as many patients have one or more bowel movement a day. More commonly, patients present with hard stool, straining, incomplete feeling, bloating and other dyspeptic symptoms. Physicians should consider CC in these situations and when patients are found to use laxative containing supplements. In the absence of alarm features physicians may start with a 2-4 week therapeutic trial of available pharmacological agents including osmotic, stimulant and enterokinetic agents. Where safe to do so, physicians should consider regular (as opposed to on demand dosing), combination treatment and continuous treatment for at least 4 weeks. If patients do not achieve satisfactory response, they should be referred to tertiary centers for physiological evaluation of colonic transit and pelvic floor function. Surgical referral is a last resort, which should be considered only after a thorough physiological and psychological evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Colon cancer is the second leading cause of cancer-related death in the United States. The considerable mortality from colon cancer is due to metastasis to other organs, mainly the liver. In the management of colon cancer, early detection and targeted therapy are crucial. In this study, we aimed to establish a versatile theranostic system for early tumor detection and targeted tumor therapy by using poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) which can selectively accumulate in tumor tissue. For the diagnostic application, a near-infrared fluorescence (NIRF) imaging dye (Cy 5.5) was chemically conjugated onto the HA backbone of P-HA-NPs. After intravenous injection of Cy5.5-P-HA-NPs into the tumor-bearing mice, small-sized colon tumors as well as liver-implanted colon tumors were effectively visualized using the NIRF imaging technique. For targeted therapy, we physically encapsulated the anticancer drug, irinotecan (IRT), into the hydrophobic cores of P-HA-NPs. Owing to their notable tumor targeting capability, IRT-P-HA-NPs exhibited an excellent antitumor activity while showing a reduction in undesirable systemic toxicity. Importantly, we demonstrated the theranostic application using Cy5.5-P-HA-NPs and IRT-P-HA-NPs in orthotopic colon cancer models. Following the systemic administration of Cy5.5-P-HA-NPs, neoplasia was clearly visualized, and the tumor growth was effectively suppressed by intravenous injection of IRT-P-HA-NPs. It should be emphasized that the therapeutic responses could be simultaneously monitored by Cy5.5-P-HA-NPs. Our results suggest that P-HA-NPs can be used as a versatile theranostic system for the early detection, targeted therapy, and therapeutic monitoring of colon cancer. [Copyright &y& Elsevier]

Objective. Few studies have assessed the diagnostic efficacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and/or trucut biopsy (TCB) in patients with rectal and perirectal lesions. We aimed to evaluate the diagnostic utility of EUS-FNA and/or TCB in patients with rectal and perirectal lesions. We also assessed their influence on the management and clinical course of these patients. Material and methods. We performed EUS-FNA and/or TCB in 11 consecutive patients (4 men and 7 women, 33-69 years) with rectal and perirectal lesions for whom conventional diagnostic tools could not provide definitive diagnoses. Patients with definite intraluminal cancer were excluded. Results. The 11 patients underwent 12 procedures, with 9 being EUS-FNA alone and 3 being EUS-FNA and TCB. Seven patients had rectal lesions and four had perirectal lesions. Initial EUS-FNA and/or TCB established a diagnosis of malignancy in five patients and of benign lesions in four. EUS-FNA plus TCB confirmed malignant lymphoma after diagnostic failure of initial EUS-FNA in one patient. In one other patient with suspicious secondary linitis plastica, EUS-FNA could not establish a definitive diagnosis. Correct diagnoses were obtained in 10 out of 11 patients who underwent EUS-FNA and/or TCB. EUS-FNA and/or TCB changed clinical courses, which included avoidance of unnecessary surgeries, having a chance of anal sphincter-saving surgeries, and timely administration of chemotherapy. No serious complications related to the use of EUS-FNA or TCB were evident. Conclusion. EUS-FNA and/or TCB are useful in the diagnostic evaluation of and appropriate therapeutic plan in patients with rectal and perirectal lesions. [ABSTRACT FROM AUTHOR]

Abstract: Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in arachidonic acid cascade, plays a key role in the biosynthesis of prostaglandin E2 (PGE2) upon inflammatory insults. Overproduction of PGE2 stimulates proliferation of various cancer cells, confers resistance to apoptosis of cancerous or transformed cells, and accelerates metastasis and angiogenesis. Excess PGE2 undergoes metabolic inactivation which is catalyzed by NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). In this context, 15-PGDH has been speculated as a physiological antagonist of COX-2 and a tumor suppressor. Thus, overexpression of 15-PGDH has been known to protect against experimentally induced carcinogenesis and renders the cancerous or transformed cells susceptible to apoptosis by counteracting oncogenic action of PGE2. In contrast, silence of 15-PGDH is observed in some cancer cells, which is associated with epigenetic modification, such as DNA methylation and histone deacetylation, in the promoter region of 15-PGDH. A variety of compounds capable of inducing the expression of 15-PGDH have been reported, which include the histone deacetylase inhibitors, nonsteroidal anti-inflammatory drugs, and peroxisome proliferator-activated receptor-gamma agonists. Therefore, 15-PGDH may be considered as a novel molecular target for cancer chemoprevention and therapy. This review highlights the role of 15-PGDH in carcinogenesis and its regulation. [Copyright &y& Elsevier]

Objective. Recent studies have suggested that the clinical characteristics and genetic background of Crohn's disease (CD) patients differ between Asian and Caucasian individuals. However, the clinical features and course of CD in Asian patients remain unclear. Therefore, we investigated the clinical features and long-term prognosis of CD in a Korean population. Material and methods. We retrospectively analyzed 278 Korean patients with CD first diagnosed at the Asan Medical Center between March 1991 and February 2007. Results. The male-to-female ratio was 2.2:1 and the median age at diagnosis was 23 years. The median duration of follow-up was 71 months (range, 1–210 months). At diagnosis, 187 patients (67.3%) had disease in both small bowel and colon, 68 (24.4%) had isolated small bowel disease, and 23 (8.3%) had isolated colonic disease. The number of patients with stricturing or penetrating behavior as defined by the Montreal classification increased from 87 (31.3%) at diagnosis to 141 (50.7%) at final evaluation. One hundred and thirty patients (46.8%) experienced perianal fistulas before and/or after diagnosis of CD. A total of 71 patients (25.5%) underwent intestinal resection and the cumulative probability of intestinal resection after 1, 5, and 10 years was 15.5%, 25.0%, and 32.8%, respectively. Conclusions. Korean CD patients differed from Western patients in gender distribution, disease location, and perianal fistula occurrence. Korean CD patients may also have better clinical courses than Western patients, as indicated by the lower intestinal resection rate. [ABSTRACT FROM AUTHOR]

Abstract: Germline mutations within the adenomatous polyposis coli (APC) gene are associated with familial adenomatous polyposis (FAP), an autosomal dominant disease predisposing individuals to colorectal cancer. Identification of APC mutations has important implications for genetic counseling and management of FAP patients. We examined the APC mutation status of 10 Korean FAP patients by polymerase chain reaction–direct sequencing method and found six APC mutations, including three novel mutations. Testing for MUTYH mutation was done for FAP patients in whom no mutation in the APC gene was identified. Three novel mutations (c.1654_1663delTCTTGGCGAG, c.3709C>T, and c.6092_6094delinsTT) and three previously reported mutations (c.3631_3632delAT, c.4438C>T, and c.4612_4613delGA) were detected. The MUTYH mutation was not detected in any of the four FAP patients without an APC mutation. This finding of three novel mutations in a group of Korean FAP patients broadens the spectrum of APC mutations. [Copyright &y& Elsevier]

Background: Although the diagnostic and therapeutic values of double balloon endoscopy (DBE) have been investigated, the subjective tolerability to DBE has not been assessed. We aimed to evaluate patients' tolerability to DBE.Methods: We prospectively enrolled patients who underwent DBE. For the comparison of tolerability to DBE with that to esophagogastroduodenoscopy (EGD) and colonoscopy, those who had not undergone EGD nor colonoscopy were excluded. A total of 52 patients were included. All procedures were performed under conscious sedation with midazolam with or without pethidine. Patients' tolerability to DBE, EGD, and colonoscopy was assessed through an interview with a questionnaire using a 10-point Likert scale.Results: A total of 36 patients underwent both antegrade DBE and EGD under conscious sedation. The level of abdominal pain during procedures, the level of post-procedural abdominal discomfort, and the proportion of patients with persistent abdominal discomfort until the next morning were higher in antegrade DBE. However, when analyzed in 16 patients who had good quality of sedation, the differences in the level of abdominal pain during procedures and the persistent abdominal discomfort until the next morning disappeared. A total of 23 patients underwent both retrograde DBE and colonoscopy under conscious sedation. Tolerability parameters were not different between retrograde DBE and colonoscopy. Serious complications, including hemodynamic instability, did not occur during all procedures.Conclusion: Patients tolerated DBE well. DBE may be performed as comfortably as EGD and colonoscopy if the quality of sedation is good enough. [ABSTRACT FROM AUTHOR]

Background: There is no consensus regarding the degree of healing of endoscopic submucosal dissection (ESD)-induced ulcers and the optimal duration of proton pump inhibitor (PPI) treatment.Aim: To evaluate the degree of healing and the factors associated with healing of ESD-induced ulcers after PPI therapy for 4 weeks.Methods: Fifty-six patients who underwent complete ESD for adenoma or early gastric cancer were enrolled. All patients underwent follow-up endoscopy to evaluate the degree of ulcer healing after pantoprazole therapy (40 mg per day) for 4 weeks. We evaluated change in size of ESD-induced ulcers between baseline and 4 weeks, and correlated relevant factors with degree of healing of small and large ulcers.Results: At follow-up, 28 (50%) patients had large ulcers (area > 10 mm(2)). Ulcer size at 4 weeks was closely correlated with initial ulcer size (P < 0.001) and abruptly increased when initial ulcer size was larger than 4 cm. Comorbidity, procedure time, and initial specimen size were significantly associated with healing rate, but multivariate analysis showed that initial ulcer size was the only significant parameter (P < 0.015).Conclusions: Healing degree of ESD-induced ulcers at 4 weeks is dependent on initial ulcer size, indicating that duration of treatment with PPI should be dependent on initial ulcer size. [ABSTRACT FROM AUTHOR]

Backgrounds: It is not clear when and how frequently surveillance endoscopy should be performed after colorectal endoscopic submucosal dissection (ESD). We aimed to suggest a surveillance endoscopy strategy by investigating the cumulative local recurrence rates and identifying risk factors for local recurrence after colorectal ESD. Methods: We reviewed the medical records of 770 patients who underwent colorectal ESD for 778 lesions at our institution from 2005 to 2016. We investigated the cumulative local recurrence rates and risk factors for local recurrence. Results: Local recurrence developed in 12 (1.5%) of 778 lesions during the follow-up period of 37.4 ± 31.7 months. The one-, three-, and five-year cumulative local recurrence rates were 0.4%, 1.7%, and 2.2%, respectively. The risk factors for local recurrence were piecemeal resection (odds ratio (OR) 3.948, 95% confidence interval (CI) 1.164–13.385; p = 0.028) and histological incomplete resection (OR 8.713, 95% CI 2.588–29.334; p < 0.001). Local recurrence tended to develop frequently after ESD of early cancers. Conclusions: Short-term surveillance endoscopy should be recommended after piecemeal ESD, histological incomplete resection, and ESD of early colorectal cancers. Surveillance endoscopy with longer intervals can be suggested after en bloc ESD with the histological complete resection of benign colorectal tumors. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that describes a case of the development of vesicoileal fistula as a complication of postoperative radiation therapy for cervical cancer.

OBJECTIVES: The aims of this prospective study were to document the incidence of colon immediate postpolypectomy bleeding (IPPB) according to grade, and to identify potential risk factors of IPPB in patients who have received complete colonoscopy and polypectomy because of a colorectal polyp. METHODS: This was a prospective, cross-sectional study of 5,152 patients treated at 11 tertiary medical centers between July 2003 and July 2004. Patient-related, polyp-related, and procedure-related variables were evaluated as potential risk factors for IPPB. IPPB was defined as a bleeding occurring during the procedure and was graded as G1–G4. Risk factors associated with IPPB were analyzed by univariate and multivariate logistic regression analysis. RESULTS: A total of 9,336 colonic polyps were removed in 5,152 patients, and 262 (2.8%) colorectal polyps in 215 patients presented with IPPB. Polyp-based multivariate analysis revealed that old age (≥65 yr), comorbid cardiovascular or chronic renal disease, anticoagulant use, polyp size greater than 1 cm, gross morphology of polyps such as pedunculated polyp or laterally spreading tumor, poorer bowel preparation, cutting mode of the electrosurgical current, and the inadvertent cutting of a polyp before current application were significant risk factors for IPPB. CONCLUSION: Nine factors have been found to be associated with IPPB and polypectomy should be undertaken with caution under these conditions. [ABSTRACT FROM AUTHOR]