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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Background 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: 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]

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 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: 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]

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]

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]

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]

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]

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: Early and accurate detection of adenomatous colonic polyps is a major concern in the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging with optical probes targeting specific peptides enables the noninvasive visualization and characterization of lesions. Matrix metalloproteinases (MMPs) are known to play an important role in tumorigenesis and tumor progression.Aim: To investigate the effectiveness of NIRF imaging, with a novel MMP-activatable probe based on a polymeric nanoparticle platform, in the colon cancer models.Methods: We used an azoxymethane (AOM)-induced mouse colon cancer model resembling human sporadic colon cancer and an MMP-positive xenograft tumor model. MMP expression was evaluated by Western blotting, real-time PCR, and immunohistochemical staining. NIRF imaging was performed with a novel MMP-activatable probe, an MMP-inactivatable probe, and saline. In addition, we observed the change of NIRF signal intensity after intratumoral administration of an MMP-inhibitor.Results: Multiple tumors with various sizes developed in AOM-treated mouse colons, progressing from adenomas to adenocarcinomas, with MMP expression progressively increasing in the normal-adenoma-adenocarcinoma sequence. In mice injected with the MMP-activatable probe, the NIRF signal also increased in this sequence and was highly correlated with MMP expression (p < 0.001). Tumor-background-ratios (TBR) of adenocarcinoma to adjacent normal mucosa by a novel probe were significantly higher than that of adenoma (p < 0.001). In both the AOM and xenograft models, NIRF signals of tumors decreased after treatment with an MMP-inhibitor.Conclusions: NIRF imaging using a polymeric nanoparticle-based probe may be useful for detecting early stage disease and for assessing treatment response. [ABSTRACT FROM AUTHOR]

Background and Aims: Researchers have not clearly described the clinical and pathogenetic features of hypoganglionosis and adult-onset Hirschsprung's disease, which cause pseudo-obstruction or intractable constipation. We conducted this study to explore these features of hypoganglionosis and adult-onset Hirschsprung's disease in Korean patients.Methods: We enrolled 24 patients pathologically confirmed as having hypoganglionosis and 11 as having adult-onset Hirschsprung's disease. We recruited 26 subjects who had undergone operation for nonobstructive colon cancer and 45 healthy volunteers as controls. We described their clinical features, investigated ganglion cells and interstitial cells of Cajal (ICC), and analyzed RET, EDNRB, EDN3, and SOX10 genes.Results: We classified hypoganglionosis patients into two groups: type I (focal type, n = 13), with focally narrowed transition zone (TZ); and type II (diffuse type, n = 11), without transition zone. Hypoganglionosis patients had significantly fewer ganglion cells than the controls, and those cells were scarcer in the transition zone than in the proximal dilated area (P < 0.05). The ICC numbers in both diseases were significantly lower than in controls; however, they were similar between transition zone and the proximal dilated area in hypoganglionosis. In adult-onset Hirschsprung's disease, two significant intronic RET polymorphic variants, IVS14-24G>A and IVS19+47T>C, were significantly associated with adult-onset Hirschsprung's disease (P = 0.0122 and 0.0295, respectively), but not with hypoganglionosis.Conclusions: Hypoganglionosis and adult-onset Hirschsprung's disease have different pathophysiologic characteristics, although their clinical presentations are similar. We suggest that there are two subgroups of hypoganglionosis: those with or without a focally narrowed transition zone with a profoundly diminished number of ganglion cells. [ABSTRACT FROM AUTHOR]

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]

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]

OBJECTIVE:To better understand the extent to which chemokines participate in the mucosal inflammatory response in patients with ulcerative colitis (UC), we assessed the expression of an array of chemokines in the colonic mucosa of UC patients and evaluated the effect of corticosteroids on their expression.METHODS:Colonic mucosal biopsy specimens were obtained from 15 patients with UC and 12 normal controls. Messenger RNA levels for 10 chemokines were quantitated by reverse transcription polymerase chain reaction using synthetic standard RNAs. The biopsy specimens were also cultured in the presence or absence of tumor necrosis factor α (TNFα) and/or dexamethasone, and secreted chemokines in culture supernatants were assayed by ELISA.RESULTS:The messenger RNA expression of C-X-C (interleukin 8, growth-related α [GROα], GROβ, GROγ, epithelial cell-derived neutrophil activator 78, and interferon-γ-inducible protein 10) and C-C (monocyte chemotactic protein 1, macrophage inflammatory protein 1β, and RANTES [regulated on activation, normal T-cell expressed and secreted]) but not C (lymphotactin) chemokines was significantly higher in the affected mucosa of UC patients than in the unaffected mucosa of UC patients or in the normal mucosa of normal controls. The degree of increased expression was more prominent in the C-X-C than in the C-C chemokines. Further, the secretion of interleukin 8, GROα, epithelial cell-derived neutrophil activator 78, and monocyte chemotactic protein 1 was higher in UC patients than in normal controls, induced significantly by TNFα, and downregulated by dexamethasone. Secretions of macrophage inflammatory protein 1β and RANTES also showed a trend toward an increase in UC, induction by TNFα, and downregulation by dexamethasone, but it did not reach statistical significance.CONCLUSIONS:The increased expression of a variety of chemokines in UC and their downregulation by dexamethasone suggest that chemokines may play an important role in the immunopathogenesis of UC. [Copyright &y& Elsevier]

Recently, several authors have reported that Helicobacter pylori DNA has been found in human bile. The aim of this study is to investigate the presence of H. pylori in the biliary tree of Koreans, including the bile, biliary epithelium, and gallstones. This study analyzed intrahepatic bile, bile duct tissue, and gallstones from 43 patients with hepatobiliary disease (PTCS group), gallbladder bile and tissue from 23 patients with gallbladder disease (CCT group), and eight patients without hepatobiliary disease (control group). H. pylori was examined by PCR with two different primers. PCR was positive in 4/43 (9.3%) by 26 kDa protein antigen primer and in 5/43 (11.6%) by urease A gene primer in bile from the PTCS group. However, in intrahepatic duct tissue, PCR was positive in only one case. PCR of gallbladder bile, tissue, and intrahepatic duct stones was negative. Upon intrahepatic bile analysis, the pH was significantly lower in PCR-positive than in negative cases (P < 0.05). In conclusion, H. pylori DNA may be present in the bile when there are certain environmental changes, such as lowered pH; however, H. pylori does not colonize the bile duct epithelium. We could find no pathogenetic role for H. pylori in the formation of hepatolithiasis. [ABSTRACT FROM AUTHOR]

We report a case of Crohn's disease with low serum zinc concentration in a 26-year-old woman. She demonstrated acrodermatitis enteropathica and decreased visual acuity during total parenteral nutrition. Subsequent intravenous zinc supplementation resulted in alleviation of the skin lesions and improvement of visual acuity. This case supports the notion that depressed serum zinc in Crohn's disease may cause clinical manifestations, such as acrodermatitis enteropathica and retinal dysfunction, which may be correctable with zinc supplementation. [ABSTRACT FROM AUTHOR]

To clarify the epidemiological characteristics of gallstone disease in Korea and to evaluate the chronological changes in gallstone disease, the authors performed this first prospective nationwide cooperative study. The subjects were 1263 gallstone patients who were admitted at 19 hospitals in Korea from February to July 1997. Questionnaires were recorded on 1263 patients and gallstones were harvested from 1133 patients. The proportion of patients with gallbladder (GB), common bile duct (CBD), and intrahepatic duct (IHD) stones among total gallstone patients was 64.0%, 21.9%, and 14.1%, respectively. GB stones were categorized as cholesterol (58.1%), black pigment (25.2%), and brown pigment (12.1%) stones. CBD stones were classified as brown pigment (76.1%), cholesterol (18.4%), and black pigment (3.5%) stones. IHD stones were classified as brown pigment (61.4%) and mixed (35.6%) stones. Intrahepatic mixed stones had mean cholesterol and bilirubin contents of 63.4 +/- 20.8% and 23.1 +/- 9.9%, respectively. In contrast, IHD brown pigment stones had mean cholesterol and bilirubin contents of 35.1 +/- 20.5% and 39.6 +/- 17.4%, respectively. Our study showed that the type and composition of gallstones in Korea was somewhat different compared with those in the West. This study also demonstrated that there have been chronological changes in the type and composition of gallstones when compared with previous domestic data. Another nationwide cooperative study may be needed to elucidate and confirm the changing pattern of gallstone disease. [ABSTRACT FROM AUTHOR]

15-hydroxyprostaglandin dehydrogenase (15-PGDH), the rate-limiting enzyme in prostaglandin E2 degradation, is decreased in gastric cancers and microRNA (miR)-21 is one of the regulators. We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic submucosal dissection (ESD) and gastric cancer cell lines. Expression of 15-PGDH and cyclooxygenase-2 as well as the promoter methylation of 15-PGDH were evaluted. CRISPR, miR-21 transfection, proliferation and apoptosis assays were also done. We observed significant decreases in 15-PGDH expression but no promoter methylation was detected in any ESDs. 15-PGDH suppression by CRISPR induced enhanced growth kinetics. miR-21, which was detected in high level in gastric tumors from the TGCA data, caused increased proliferation, decreased apoptosis. miR-21 overexpression was confirmed with CISH and RT-PCR in the ESDs. Loss of 15-PGDH occurs at the very early stage of gastric adenocarcinoma by miR-21. H. pylori infection may affect miR-21 up regulation. Maintaining 15-PGDH enzyme activity could be a new strategic measure in preventing gastric cancer especially tubular adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review recently published diagnostic methods that use high-resolution (HR-) or high-definition- (HD-) anorectal manometry (ARM) techniques.Recent Findings: The integrated pressurized volume (IPV) is a new measure based on spatiotemporal plots obtained from HR-ARM. The IPV may be clinically useful for improving the prediction of abnormal balloon expulsion test in patients with constipation and for discriminating patients with anorectal disorders from asymptomatic controls. Combination of IPV parameters was superior to conventional manometric parameters in predicting the responsiveness to biofeedback therapy. Moreover, several novel parameters including the HR-ARM resting integral, HR-ARM squeeze profile, and anorectal asymmetry index may each be useful as predictive factors for identifying patients with fecal incontinence.Summary: HR- and HD-ARM are increasingly performed worldwide for evaluation of anorectal function. Here, we describe new metrics whose clinical significance has not been fully established. Further standardization and validation of these metrics could provide clinically important new information and could help improve our understanding of the pathophysiology of anorectal disorders. [ABSTRACT FROM AUTHOR]

The original version of this Article contained errors in Figs. 4, 5, and 6. In Fig. 4d, the x-axis label incorrectly read ‘blank, +, blank, +’, and in Fig. 5e, the bars of the second graph from the left were coloured blue-orange-blue-orange. Both of these errors have been fixed in the PDF and HTML versions of the Article. Furthermore, in Fig. 6a, the right-hand image of AGS cells treated with 5 µM DY131 was inadvertently replaced with a duplicate of the left-hand image. The correct version of this figure panel appears in the Author Correction associated with this Article. For transparency, the error has not been corrected in the PDF or HTML versions of the Article. [ABSTRACT FROM AUTHOR]

The principle factors underlying gastric cancer (GC) development and outcomes are not well characterized resulting in a paucity of validated therapeutic targets. To identify potential molecular targets, we analyze gene expression data from GC patients and identify the nuclear receptor ESRRG as a candidate tumor suppressor. ESRRG expression is decreased in GC and is a predictor of a poor clinical outcome. Importantly, ESRRG suppresses GC cell growth and tumorigenesis. Gene expression profiling suggests that ESRRG antagonizes Wnt signaling via the suppression of TCF4/LEF1 binding to the CCND1 promoter. Indeed, ESRRG levels are found to be inversely correlated with Wnt signaling-associated genes in GC patients. Strikingly, the ESRRG agonist DY131 suppresses cancer growth and represses the expression of Wnt signaling genes. Our present findings thus demonstrate that ESRRG functions as a negative regulator of the Wnt signaling pathway in GC and is a potential therapeutic target for this cancer. Very little is known regarding the molecular mechanisms involved in gastric cancer development. Here the authors show estrogen-related receptor gamma (ESRRG) is a tumor suppressor in gastric cancer and suggest the mechanism of this tumor suppression function involves the inhibition of Wnt signaling. [ABSTRACT FROM AUTHOR]