Risk factors and management of iatrogenic colorectal perforation in diagnostic colonoscopy: a single-center cohort study.

BACKGROUND AND AIMS: Diagnostic colonoscopy plays a central role in colorectal cancer screening programs. We analyzed the risk factors for perforation during diagnostic colonoscopy and discussed the treatment outcomes. METHODS: We performed a retrospective analysis of risk factors and treatment outcomes of perforation during 74,426 diagnostic colonoscopies between 2013 and 2018 in a tertiary hospital. RESULTS: A total of 19 perforations were identified after 74,426 diagnostic colonoscopies or sigmoidoscopies, resulting in a standardized incidence rate of 0.025% or 2.5 per 10,000 colonoscopies. The majority (15 out of 19, 79%) were found at the sigmoid colon and recto-sigmoid junction. Perforation occurred mostly in less than 1000 cases of colonoscopy (16 out of 19, 84%). In particular, the incidence of perforation was higher in more than 200 cases undergoing slightly advanced colonoscopy rather than beginners who had just learned colonoscopy. Old age (≥ 70 years), inpatient setting, low body mass index (BMI), and sedation status were significantly associated with increased risk of perforation. Nine (47%) of the patients underwent operative treatment and ten (53%) were managed non-operatively. Patients who underwent surgery were often diagnosed with delayed or concomitant abdominal pain. Perforations of rectum tended to be successfully treated with endoscopic clipping. CONCLUSIONS: Additional precautions are required to prevent perforation in elderly patients, hospital settings, low BMI, sedated patients, or by a doctor with slight familiarity with endoscopies (but still insufficient experience). Endoscopic treatment should be actively considered if diagnosis is prompt, abdominal pain absent, and especially the rectal perforation is present.

Risk Prediction of Post-Endoscopic Submucosal Dissection Coagulation Syndrome.

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been popular worldwide to treat laterally spreading tumors and large polyps. Post-ESD coagulation syndrome (PECS) is more common than the two major ESD-related complications, perforation, and bleeding. The aim of this study was to assess the prevalence of PECS, identify the risk factors for PECS, and create a risk prediction model for PECS. METHODS: Retrospective cross-sectional study analyzed a total of 986 patients who underwent colorectal ESD. Logistic regression models were used to assess risk factors with PECS. Each risk factor was scored, and the 3-step risk stratification index of prediction model was assessed. RESULTS: The prevalence of PECS was 21.4% (95% confidence interval [CI] = 18.9-24.1%). The risk factors of PECS in the multivariate logistic regression were tumor size (+1 cm: odds ratio [OR], 1.29; 95% CI, 1.16-7.09), cecal lesion (OR, 1.96; 95% CI, 1.09-1.53), procedure time (+30 min: OR, 1.19; 95% CI, 1.02-1.39), and ESD with snaring (OR, 0.64; 95% CI, 0.43-0.95). Applying a simplified weighted scoring system based on adjusted OR increments of 1, the risk of PECS was 12.3% (95% CI, 0.3-16.0%) for the low-risk group (score ≤4) and was 36.0% (95% CI = 29.4-43.2%) for the high-risk group (score ≥8). Overall discrimination (C-statistic = 0.629; 95% CI = 0.585-0.672) and calibration (p = 0.993) of the model were moderate to good. CONCLUSION: PECS occurs frequently, and the prediction model can be helpful for effective treatment and prevention of PECS.

International consensus on the management of large (≥20 mm) colorectal laterally spreading tumors: World Endoscopy Organization Delphi study.

OBJECTIVES: There have been significant advances in the management of large (≥20 mm) laterally spreading tumors (LSTs) or nonpedunculated colorectal polyps; however, there is a lack of clear consensus on the management of these lesions with significant geographic variability especially between Eastern and Western paradigms. We aimed to provide an international consensus to better guide management and attempt to homogenize practices. METHODS: Two experts in interventional endoscopy spearheaded an evidence-based Delphi study on behalf of the World Endoscopy Organization Colorectal Cancer Screening Committee. A steering committee comprising six members devised 51 statements, and 43 experts from 18 countries on six continents participated in a three-round voting process. The Grading of Recommendations, Assessment, Development and Evaluations tool was used to assess evidence quality and recommendation strength. Consensus was defined as ≥80% agreement (strongly agree or agree) on a 5-point Likert scale. RESULTS: Forty-two statements reached consensus after three rounds of voting. Recommendations included: three statements on training and competency; 10 statements on preresection evaluation, including optical diagnosis, classification, and staging of LSTs; 14 statements on endoscopic resection indications and technique, including statements on en bloc and piecemeal resection decision-making; seven statements on postresection evaluation; and eight statements on postresection care. CONCLUSIONS: An international expert consensus based on the current available evidence has been developed to guide the evaluation, resection, and follow-up of LSTs. This may provide guiding principles for the global management of these lesions and standardize current practices.

A GLP-1/GLP-2 receptor dual agonist to treat NASH: Targeting the gut-liver axis and microbiome.

BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. APPROACH AND RESULTS: C57BL/6J mice were fed a choline-deficient high-fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc fusion (GLP1/2-Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis. CONCLUSIONS: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn's disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn's disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn's disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0-6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0-6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48-26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with "cannot be passed" compared to the cases without stenosis (HR 12.34; 95% CI 1.66-91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

The optimal surgery timing after stenting in colorectal cancer patients with malignant obstruction: additionally compared with emergency surgery.

BACKGROUND: This study aimed to determine short-term and long-term outcomes according to time intervals after stenting and compared them with those of emergency surgery (ES) in colorectal cancer (CRC) with malignant obstruction. METHODS: CRC with malignant obstructions was reviewed retrospectively between January 2008 and July 2018. Of a total of 539 patients who visited the emergency room and underwent ES, 133 were enrolled in the ES group. Of a total of 567 patients who initially received stenting and subsequently underwent elective surgery, 220 were enrolled in the SEMS group. The interval between SEMS placement and elective surgery was classified as < 11 days, 11-17 days, and > 17 days. RESULTS: For those who received SEMS (n = 220), those with a time interval of 11-17 days (n = 97) had fewer hospital days than those with a time interval of < 11 days (n = 68) (8 days vs. 15 days) and less stoma formation than those with a time interval of > 17 days (n = 55) (1.0% vs. 14.6%). Multivariable analysis revealed a decreased risk of death for the group with a time interval of 11-17 days (20.6%) compared to the ES group (31.6%) (hazard ratio: 0.48; 95% confidence interval: 0.24-0.97). Disease-free survival was comparable between the SEMS and ES groups regardless of the time interval (log-rank p = 0.52). CONCLUSIONS: The time interval of 11-17 days after stenting to elective surgery appeared to be associated with the most favorable outcomes.

Specificity of clinical decision support tools for vedolizumab and ustekinumab in biologically naïve patients with Crohn's disease.

BACKGROUND AND AIMS: Clinical decision support tools (CDST) were developed to predict drug response to various biological treatments for Crohn's disease (CD). This study investigated whether CDSTs for vedolizumab (V-CDST) and ustekinumab (U-CDST) can be used as prognostic or drug-specific markers to predict response. METHODS: A hypothetical scenario involving 872 patients with CD who were exposed to the first biological therapy at Samsung Medical Center between 1995 and 2020 is presented. V-CDST & U-CDST were calculated based on clinical and laboratory data immediately before the first biologic was initiated. The Cumulative Link Mixed Model (CLMM) test, weighted Kappa and plot, and Spearman's correlation was used to determine the degree of agreement and difference between the two tools. RESULTS: 25% of all patients diagnosed with biologically naïve CD were categorized into different probability groups using V-CDST and U-CDST. The difference between the two tools was significantly based on a two-sample paired ordinal test with Cumulative Link Mixed Model (CLMM) (p-value < .001). Concordance between the two tools with a total of 654 subjects (75% of all patients) showed a similar probability (weighted Kappa: 0.47, 95% CI: 0.41-0.52). CONCLUSIONS: V-CDST and U-CDST are useful in selecting vedolizumab or ustekinumab in 25% of biologically naïve CD patients in our hypothetical scenario.

Long-term prognosis of curative endoscopic submucosal dissection for early colorectal cancer according to submucosal invasion: a multicenter cohort study.

BACKGROUND: Endoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis. METHODS: This multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence. RESULTS: The median follow-up period was 53.8 (12-138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% (p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248). CONCLUSIONS: Patients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.

Recurrence pattern and surveillance strategy for rectal neuroendocrine tumors after endoscopic resection.

BACKGROUND AND AIM: Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. METHODS: We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3). RESULTS: A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38-2.23). Extracolonic metastasis was not detected in this study. CONCLUSION: Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non-metastatic rectal NETs. However, regular endoscopic follow-up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs.

Epithelial Regeneration Ability of Crohn's Disease Assessed Using Patient-Derived Intestinal Organoids.

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn's disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.

Helicobacter pylori Infection and the Development of Advanced Colorectal Neoplasia.

BACKGROUND: An association between Helicobacter pylori infection and colorectal neoplasia has been reported in cross-sectional studies. GOALS: We examined the association between H. pylori infection and the development of advanced colorectal neoplasia (AN) in a screening cohort. STUDY: We identified 3753 adults, who underwent screening and subsequent surveillance colonoscopies. The primary outcome was the development of metachronous AN, as confirmed by surveillance colonoscopy. H. pylori infection status was assessed by an H. pylori-specific immunoglobulin G antibody test. Sensitivity analysis was also performed by H. pylori infection status on the basis of histology. RESULTS: During a median follow-up of 41 months, the incidence of AN was 3.2% and 1.7% in participants with and without H. pylori infection, respectively. In multivariable analysis adjusted for age, body mass index, smoking status, alcohol intake, family history of colorectal cancer, and baseline adenoma characteristics, the hazard ratio [95% confidence interval (CI)] for metachronous AN was 1.74 (1.11-2.73) in participants with H. pylori seropositivity, compared with those without H. pylori seropositivity. The association was consistent with H. pylori infection status on the basis of histology (adjusted hazard ratio, 3.51; 95% CI, 1.64-7.51). In the subgroup analysis, the positive association was observed in both no-adenoma and adenoma removal subgroups. CONCLUSIONS: In a cohort study, H. pylori infection was associated with an increased risk of AN development. This association was consistent in both the serological and histologic assessment of H. pylori infection. Prospective studies are necessary to determine whether H. pylori eradication can reduce the risk of colorectal neoplasia.

Combination of bisacodyl suppository and 1 L polyethylene glycol plus ascorbic acid is a non-inferior and comfortable regimen compared to 2 L polyethylene glycol plus ascorbic acid.

BACKGROUND AND AIM: Appropriate bowel cleansing before colonoscopy is an important factor in increasing the detection rate of lesions. Low-volume polyethylene glycol (PEG) plus ascorbic acid (PEG-Asc) reduces the dosage of bowel preparation agent, but still presents discomfort to patients. The primary aim of the present study was to compare the efficacy of bowel cleansing between 2 L PEG-Asc (control) and 1 L PEG-Asc with bisacodyl suppository (suppository) groups, and the secondary aim was to investigate complications and tolerability between the two groups. METHODS: This was a single-center prospective randomized controlled study. We identified 168 patients scheduled for colonoscopy between August 2017 and January 2018 and randomly assigned them to the control or to the suppository groups. Efficacy of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS), and side-effects were surveyed using questionnaires. RESULTS: No significant difference was detected in baseline characteristics including insertion and withdrawal times, and adenoma detection rates between the two groups. Total BBPS score was 7.93 ± 1.06 and 7.74 ± 1.02 in the control and suppository groups, respectively (P = 0.22). Incidence of abdominal pain and nausea was not statistically different, whereas that of sleep disturbance and anal discomfort was higher in the control group. (P = 0.00). CONCLUSIONS: One liter PEG-Asc with bisacodyl suppository resulted in an equivalent bowel-cleansing outcome with reduced patient discomfort compared to 2 L PEG-Asc. Therefore, PEG-Asc with bisacodyl suppository represents a potential alternative and increases patient compliance with bowel preparation.

C-Reactive protein reduction rate following initiation of anti-tumor necrosis factor α induction therapy predicts secondary loss of response in patients with Crohn's disease.

Background/aim: The objective of this study is to identify clinical predictors of primary non-response (PNR) and secondary loss of response (LOR), in Crohn's disease (CD) patients treated with anti-tumor necrosis factor α (anti-TNF) agents. Methods: This retrospective, longitudinal, and observational cohort study included 283 patients with CD who received anti-TNF treatments from November 2006 to July 2017 at Samsung Medical Center, Seoul, Korea. Results: A total of 212 patients with CD were eligible and based on clinical responses, divided into three groups: PNR, LOR, and responder groups. PNR occurred in 13 patients (6.1%). C-Reactive protein (CRP) level at initiation of anti-TNF (baseline CRP) was a possible predictor of PNR compared to the non-PNR group (baseline CRP >1 mg/dl, OR = 4.34, 95% CI = 1.06-17.83, p = .042). During maintenance therapy, incidence of LOR was 12.2% at 1-year, 23.6% at 2-years, 36.3% at 3-years, and 52.1% at 5-years. Combining baseline CRP level and CRP reduction rate [(CRP at 12-14 weeks-baseline CRP)/baseline CRP] was a possible predictor of 1-year LOR compared to the responder group (baseline CRP >1 mg/dl and CRP reduction rate > -70%, OR = 18.86, 95% CI = 3.40-104.55, p = .001). In the Cox hazard proportional model, a combination of baseline CRP level and CRP reduction rate was possible predictors of long-term LOR during maintenance therapy (baseline CRP >1 mg/dl and CRP reduction rate > -70%, HR = 5.84, 95% CI = 2.75-12.41, p < .001). Conclusions: Baseline CRP level and CRP reduction rate might be clinical predictors for PNR or LOR to anti-TNF in patients with CD, and could guide proper therapeutic interventions in patients with CD.

Impact of sarcopenia on the risk of advanced colorectal neoplasia.

BACKGROUND AND AIM: Sarcopenia is a pathological condition characterized by the progressive loss of muscle mass and increased amount of visceral fat. Recent evidence has revealed that sarcopenia is associated with certain diseases. However, the impact of sarcopenia on colorectal neoplasia has not been documented clearly. We studied the association between sarcopenia and advanced colorectal neoplasia in a large screening population. METHODS: This cross-sectional study included 14 024 asymptomatic adults who underwent first-time screening colonoscopy. Sarcopenia (class II) was defined as an appendicular skeletal muscle mass (ASM)/bodyweight (%) value more than two standard deviations below the mean for healthy young adults. ASM was estimated using bioelectrical impedance analysis. RESULTS: In a multivariable model adjusted for age, sex, obesity (body mass index ≥ 25), smoking status, alcohol intake, regular exercise, and family history of colorectal cancer, the odds ratio (OR) for advanced colorectal neoplasia on comparing participants with sarcopenia (class II) to those without sarcopenia (class I + II) was 1.52 (95% confidence interval [CI], 1.23-1.86). Further adjustment for metabolic parameters attenuated this association, but the association was still significant (OR, 1.34; 95% CI, 1.07-1.68). Furthermore, the multivariable (traditional risk factors)-adjusted OR associated with a 1% decrease on the introduction of ASM/weight% as a continuous variable in regression models was 1.04 (95% CI, 1.01-1.07) for advanced colorectal neoplasia. CONCLUSIONS: Our findings indicate that sarcopenia is significantly and progressively associated with the risk of advanced colorectal neoplasia. This association might be explained by metabolic factors that could be potential mediators of the effect of sarcopenia.

Risk of Metachronous Advanced Neoplasia in Patients With Multiple Diminutive Adenomas.

OBJECTIVES: Individuals with advanced adenomas or three or more adenomas have a higher risk of metachronous advanced neoplasia (AN) and are recommended to undergo surveillance colonoscopy at shorter intervals. However, it is questionable whether patients with multiple (three or more) non-advanced diminutive adenomas should be considered as high-risk. METHODS: We analyzed 5482 patients diagnosed with one or more adenomas during their first colonoscopy screening and who underwent a follow-up colonoscopy. Patients were categorized into four groups based on adenoma characteristics at baseline: Group 1, 1-2 non-advanced adenomas; Group 2, ≥3 non-advanced, diminutive (1 to 5 mm) adenomas; Group 3, ≥3 non-advanced, small (6-9 mm) adenomas; and Group 4, advanced adenomas. RESULTS: During a median follow-up of 38 months, the incidence of metachronous AN at surveillance colonoscopy was 5.6%. The incidence of AN was 3.9% in group 1, 5.9% in group 2, 10.6% in group 3, and 22.1% in group 4. The adjusted hazard ratios (HRs) [95% confidence intervals (CIs)] for metachronous AN between group 2, group 3, and group 4, and low risk group 1 were 1.71 (0.99-2.94), 2.76 (1.72-4.44), and 5.23 (3.57-7.68), respectively. Compared with group 4, the adjusted HRs (95% CIs) for group 1, group 2, and group 3 were 0.19 (0.13-0.28), 0.32 (0.18-0.59), and 0.52 (0.31-0.89), respectively. CONCLUSIONS: We found that patients with three or more non-advanced diminutive adenomas had a borderline increased risk of metachronous AN compared with patients with low risk adenomas.

Adenoma detection rate influences the risk of metachronous advanced colorectal neoplasia in low-risk patients.

BACKGROUND AND AIMS: In individuals with either no or 1 to 2 nonadvanced adenomas, future risks of advanced colorectal neoplasia (AN) vary according to clinical risk factors. However, little is known about the association between the adenoma detection rate (ADR) and the risk for metachronous AN in patients with low-risk adenomas. METHODS: We identified 7171 participants with no or 1 to 2 nonadvanced adenomas at first-time screening colonoscopy. The risk of metachronous AN was investigated at surveillance colonoscopy, according to clinical characteristics and the ADR. RESULTS: In multivariate analysis the risk for metachronous AN was strongly associated with increasing age, male sex, increasing number of adenomas, and the ADR of the endoscopist. With the ADR modeled as a continuous variable, each 1.0% increase in the rate of ADR predicted a 3.0% decrease in the risk of metachronous AN (adjusted odds ratio [OR], .97; 95% confidence interval [CI], .95-.99). With the ADR modeled using a binary cut-off (32%), the risk of metachronous AN was reduced in patients of endoscopists with an ADR ≥32% (adjusted OR, .53; 95% CI, .35-.83). Moreover, the risk of metachronous AN was reduced (adjusted OR, .66; 95% CI, .46-.95) in patients of endoscopists with an ADR in the highest tertile, compared with patients of endoscopists with ADRs in the lowest tertile. The impact of ADR on metachronous AN was significant for patients with low-risk adenomas rather than patients with no adenoma. CONCLUSIONS: In patients with low-risk adenomas, the ADR of the endoscopist was inversely associated with the risk of metachronous AN.

Survival Outcome and Risk of Metachronous Colorectal Cancer After Surgery in Lynch Syndrome.

BACKGROUND: The survival benefit of extensive colectomy is controversial in Lynch syndrome, and risk factors for metachronous colorectal cancer (CRC) after segmental colectomy are unclear. OBJECTIVE: The aim of this study was to investigate the survival outcome and risk of metachronous CRC after surgery in Lynch syndrome patients diagnosed with their first CRC. METHODS: Overall, 106 patients with Lynch syndrome who underwent surgery for CRC were included in the study. The demographics, genotype, clinicopathological characteristics of the index CRC, and follow-up data were reviewed from a single-institution Lynch syndrome database. RESULTS: Of 30 patients who underwent extensive surgery, no metachronous CRC was developed during a mean follow-up of 68.1 months. Of 76 patients who underwent segmental colectomy, 13 (17.1 %) developed metachronous CRC during a mean follow-up of 77.2 months. The cumulative risk of metachronous CRC was 8.4 % at 5 years and 20.4 % at 10 years after segmental colectomy. No difference in overall and CRC-specific survival was observed between segmental colectomy and extensive colectomy (p = 0.277 and p = 0.659, respectively). A 25 cm or longer resection of bowel decreased the risk of metachronous CRC after segmental colectomy compared with less extensive resection (hazard ratio 0.10, 95 % confidence interval 0.01-0.86). Annual surveillance colonoscopy did not decrease the risk of metachronous CRC compared with less frequent surveillance colonoscopy. Although not statistically significant, none of the MSH6 gene mutation carriers were diagnosed with metachronous CRC. CONCLUSIONS: Although no survival benefit was identified, surgeons and patients might consider extensive colectomy to prevent metachronous CRC in Lynch syndrome patients regardless of their clinicopathological characteristics.

Helicobacter pylori infection is an independent risk factor of early and advanced colorectal neoplasm.

BACKGROUND: The role of Helicobacter pylori (H. pylori) in the development of colorectal neoplasm remains controversial. We examined the association between H. pylori infection and colorectal neoplasm in a large sample of healthy participants who underwent screening colonoscopy. METHODS: A cross-sectional study of 8916 men, who participated in a regular health-screening examination that included an H. pylori-specific immunoglobulin G antibody test and colonoscopy, was conducted to evaluate the association between H. pylori and colorectal neoplasm. RESULTS: Multivariable analyses adjusted for age, body mass index, smoking status, alcohol intake, regular exercise, regular aspirin use, and family history of colorectal cancer showed that the odds ratio (OR) (95% confidence interval [CI]) for any adenoma and advanced neoplasm was 1.32 (1.07-1.61) and 1.90 (1.05-3.56) in participants with H. pylori infection and without H. pylori infection, respectively. The association persisted after further adjustment for inflammatory markers or metabolic variables including fasting blood glucose, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. Regarding the location, a positive association was confined to cases with proximal adenomas and was observed similarly in all the evaluated subgroups. CONCLUSIONS: In a large-scale study, carefully controlled for confounding factors, involving asymptomatic participants without a history of colonoscopy, H. pylori infection was significantly associated with the risk of any colorectal adenoma and advanced colorectal neoplasm. Prospective studies are necessary to determine whether H. pylori eradication can reduce this risk.

Clinical outcome after enteroscopy for small bowel angioectasia bleeding: A Korean Associateion for the Study of Intestinal Disease (KASID) multiceter study.

BACKGROUND AND AIMS: Angioectasias are the most common sources of bleeding in the small bowel. They can be treated using balloon-assisted enteroscopy (BAE). This study aimed to identify the rebleeding rate and associated factors after BAE in patients with small bowel angioectasia bleeding. METHODS: We retrospectively analyzed the records of patients with bleeding due to small bowel vascular lesion in a multicenter enteroscopy database including 1108 BAEs. Finally, in rebleeding analysis, we analyzed 66 patients with angioectasia on the basis of the Yano-Yamamoto classification. Patients who had undergone endotherapy (ET) were divided into ET (n = 45) and non-ET (n = 21) groups. Rebleeding was defined as evidence of bleeding at least 30 days after BAE. RESULTS: Fifty-three patients (80.4%) underwent only one-side enteroscopy. The most common ET was argon plasma coagulation (87.2%). During a mean follow-up duration of 24.5 months, ET and non-ET groups had rebleeding rates of 15.6% and 38.1% (P = 0.059), respectively. Median rebleeding time of ET and non-ET groups was 32.5 and 62 months, respectively. Liver cirrhosis (LC), low platelet count (< 105 /µL), and transfusions were the rebleeding-associated factors in the univariate analysis. In the multivariate analysis, the presence of LC (HR 4.064, 95% CI 1.098-15.045; P = 0.036) was the only independent rebleeding-associated risk factor. CONCLUSIONS: ET using BAE did not significantly affect the rebleeding rate in patients with small bowel angioectasia bleeding. An independent rebleeding risk factor was the presence of LC. Regardless of ET, careful long-term follow-up may be needed, especially in LC patients with small bowel angioectasia bleeding.

Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia.

The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we generated mice with disruption of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus. These mice exhibited a reduction in postweaning feeding and growth, and disrupted hyperphagic responses to NPY. Disruption of GABA release severely diminished GABAergic input to the paraventricular hypothalamic nucleus (PVH). Furthermore, disruption of GABA-A receptor function in the PVH also reduced postweaning feeding and blunted NPY-induced hyperphagia. Given the limited knowledge on postweaning feeding, our results are significant in identifying GABA release from a major subset of less appreciated hypothalamic neurons as a key mediator for postweaning feeding and NPY hyperphagia, and the PVH as one major downstream site that contributes significantly to the GABA action. Significance statement: Prevalent studies on feeding in the hypothalamus focus on well characterized, selective groups neurons [e.g., proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons], and as a result, the role of the majority of other hypothalamic neurons is largely neglected. Here, we demonstrated an important role for GABAergic projections from non-POMC non-AgRP neurons to the paraventricular hypothalamic nucleus in promoting postweaning (mainly nocturnal) feeding and mediating NPY-induced hyperphagia. Thus, these results signify an importance to study those yet to be defined hypothalamic neurons in the regulation of energy balance and reveal a neural basis for postweaning (nocturnal) feeding and NPY-mediated hyperphagia.