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.

Gut microbial signatures in clinically stable ulcerative colitis according to the mucosal state and associated symptoms.

BACKGROUND AND AIM: The gut microbiome of patients with clinically stable ulcerative colitis (UC) differs from that of healthy individuals depending on the state of the colonic mucosa, especially with or without advanced scarring; however, the underlying mechanism is unclear. Therefore, this study examined the gut microbiome compositional signatures in patients with significant mucosal scarring and UC-related symptoms. METHODS: Stool samples for gut microbiome analysis were prospectively collected from 57 patients with clinically stable UC between January 1 and December 31, 2022. Data from 57 individuals without inflammatory bowel disease (non-IBD) paired by age and sex were selected from our previous study as the control group. The fecal samples were subjected to 16S rRNA gene sequencing. Associations between gut microbiome profiles and clinical or colonoscopic assessments were examined using diversity and differential abundance analyses. RESULTS: Gut microbiome compositions between the patients with clinically stable UC and non-IBD controls differed significantly. Furthermore, gut microbiome compositions varied between the preserved and altered mucosa groups identified based on mucosal changes in the UC group. Differential abundance test of patients with UC for symptomatic remission based on stool frequency from the two-item patient-reported outcome identified several overlapping taxa specified as gut microbiome signatures, including the Enterobacteriaceae unknown genera (Enterobacteriaceae_g), Klebsiella, and several Lachnospiraceae spp. both in mucosal and symptom change analyses. CONCLUSIONS: The gut microbiome can change with mucosal changes, even in clinically stable UC, and some gut microbial signatures may explain the symptom manifestations in patients with UC showing significant mucosal changes.

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.

Efficacy and safety of split-dose bowel preparation with 1 L polyethylene glycol and ascorbate compared with 2 L polyethylene glycol and ascorbate in a Korean population: a phase IV, multicenter, randomized, endoscopist-blinded study.

BACKGROUND AND AIMS: The 1-L polyethylene glycol (PEG)-based bowel preparation agent NER1006 (Plenvu; Norgine, Harefield, UK) has shown high cleansing efficacy and tolerability in clinical trials in Europe and North America. However, no clinical trials have yet been reported in Asia. Therefore, the aim of this study was to evaluate the efficacy and safety of 1L PEG-based bowel preparation with Plenvu compared with 2L PEG plus ascorbate bowel preparation in a Korean population. METHODS: In this multicenter, endoscopist-blinded, randomized study, patients at 9 hospitals in South Korea undergoing colonoscopy received either Plenvu or 2L PEG + ascorbate (2L PEG) with a split dose. The primary endpoint was overall bowel cleansing success (Boston Bowel Preparation Scale [BBPS] score ≥2 for all segments of the colon). Secondary endpoints were high-quality bowel cleansing success (overall, BBPS score = 9; segmental colon, BPPS score = 3), polyp detection rate (PDR), and adenoma detection rate (ADR). RESULTS: Of 360 included patients, cleansing efficacy was analyzed in 346 (Plenvu, 174; 2L PEG, 172). The Plenvu group showed noninferior bowel cleansing success rates compared with 2L PEG (93.10% vs 91.86%; difference, 1.24%; 1-sided 97.5% lower confidence limit, -4.31%; Pnoninferiority < .0001; Psuperiority = .661). The Plenvu group had higher high-quality bowel cleansing success rates for overall and right-sided colon segments than the 2L PEG group (49.43% vs 37.79% [P = .029] and 60.92% vs 48.84% [P = .024], respectively). The PDR was greater with Plenvu than with 2L PEG (48.85% vs 37.79%, P = .038). However, ADR did not differ between the 2 groups (24.71% vs 20.35%, P = .331). Although treatment-emergent adverse events (TEAEs) were slightly higher in the Plenvu group than in the 2L PEG group (65.71% vs 52.91%, P = .015), most TEAEs were mild (85.55%) and most patients recovered without any management (99.23%). CONCLUSIONS: Plenvu showed noninferior overall bowel cleansing success rates comparable with 2L PEG but greater high-quality bowel cleansing in overall and right-sided colon, which might help improve the PDR in the Asian population. (Clinical trial registration number: KCT0005894.).

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.

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.

Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

OBJECTIVE: No population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based cohort. DESIGN: This Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986-2015. Disease outcomes and their predictors were evaluated. RESULTS: During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004). CONCLUSION: Korean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.

Cap-Assisted Chromoendoscopy Using a Mounted Cap Versus Standard Colonoscopy for Adenoma Detection.

OBJECTIVES: Some neoplastic lesions remain undetected on colonoscopy. To date, no studies have investigated whether combining cap-assisted colonoscopy with chromoendoscopy increases the adenoma detection rate (ADR). This study aimed to compare cap-assisted chromoendoscopy (CAP/CHROMO) with standard colonoscopy (SC) with respect to their efficacy in detecting adenomas. METHODS: This prospective, multicenter, randomized controlled trial included asymptomatic subjects aged 45-75 years who underwent colonoscopy for the first time at 14 university hospitals. Subjects were randomized to either the CAP/CHROMO group (with 0.09% indigo carmine spraying using a cap-mounted catheter at the tip of the colonoscope) or the SC group. All polyps were resected, but only histologically confirmed neoplastic lesions were considered for analysis. The primary outcome was ADR, defined as the proportion of subjects with at least 1 adenoma. RESULTS: A total of 1,905 subjects were randomized to the CAP/CHROMO (n = 948) or SC (n = 957) group at 14 centers. Subjects' demographic characteristics were similar between both groups. The CAP/CHROMO group had significantly higher ADR than the SC group (54.4% vs 44.9%, P < 0.001). Significantly, more subjects with at least 1 proximal colon adenoma were identified by CAP/CHROMO (38.6%) than by SC (31.2%) (P = 0.001). The proximal serrated polyp detection rate by CAP/CHROMO was significantly higher in the female subgroup vs SC. However, advanced ADR was not different between the CAP/CHROMO and SC groups (9.3% vs 7.6%, P = 0.180). DISCUSSION: CAP/CHROMO markedly improved the ADR and enhanced the detection of proximal adenoma. CAP/CHROMO is feasible for routine application and will allow for a more effective surveillance program.

Effects of various genetic polymorphisms on thiopurine treatment-associated outcomes for Korean patients with Crohn's disease.

AIMS: This study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea. METHODS: A total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The TPMT and NUDT15 genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to TPMT and NUDT15 genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia). RESULTS: The median duration of thiopurine treatment was 47.0 months (range 6.0-153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti-tumour necrosis factor agents were associated with thiopurine metabolite concentrations (P < .05). In the univariate analysis, the TPMT genotype was associated with 6-thioguanine level (P < .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the ATIC (rs3821353 and rs16853834), IMPDH2 (rs11706052) and ITPA (rs6139036) genes were associated with thiopurine metabolism (P < .05). Genetic polymorphisms in the ABCC5 (rs8180093) and NUDT15 genotypes were associated with leukopenia (P < .05). CONCLUSION: The results of this study may help clinicians to understand the effects of other various polymorphisms in addition to TPMT and NUDP15 in thiopurine metabolism for management of Crohn's disease patients.

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.

Long-term efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study.

BACKGROUND AND AIM: A biosimilar of infliximab, CT-P13 (Remsima®) has the potential to reduce treatment costs and enhance access to biological therapy for inflammatory bowel disease (IBD) patients. However, long-term clinical data on its use for IBD treatment are currently sparse. We aimed to investigate the long-term efficacy and safety of CT-P13 therapy in a large, real-life IBD cohort. METHODS: A total of 368 IBD patients (227 with Crohn's disease [CD] and 141 with ulcerative colitis [UC]) treated with CT-P13 at 16 referral hospitals in Korea between July 2012 and December 2017 were retrospectively analyzed. RESULTS: The cumulative retention rates at years 1, 3, and 5 were 86.1%, 68.5%, and 58.7% and 69.7%, 46.0%, and 26.7% in anti-tumor necrosis factor (TNF)-naïve CD and UC patients, respectively. The clinical response and remission rates at week 14 and at years 1, 3, and 5 were 94.3%, 92.7%, 76.8%, and 17.6% and 78.6%, 82.4%, 72.2%, and 17.6% in anti-TNF-naïve CD and 85.6%, 80.0%, 55.2%, and 6.7% and 42.6%, 59.8%, 44.2%, and 6.7% in anti-TNF-naïve UC patients, respectively. Among patients who switched from the biologic originator to CT-P13, the cumulative retention rates at years 1, 3, and 5 were 88.5%, 66.1%, and 44.8% in CD, and 73.9%, 42.5%, and 42.5% in UC patients, respectively. Significant improvements in disease activity scores were accompanied by marked reductions in inflammatory marker levels, and no unexpected adverse events including death or malignancy occurred during the study period. CONCLUSIONS: Long-term treatment with CT-P13 is effective in inducing and maintaining disease improvement and is well-tolerated in patients with IBD. CT-P13 may be a promising treatment option for IBD.

Comparison of Proton and Photon Beam Irradiation in Radiation-Induced Intestinal Injury Using a Mouse Model.

When radiotherapy is applied to the abdomen or pelvis, normal tissue toxicity in the gastrointestinal (GI) tract is considered a major dose-limiting factor. Proton beam therapy has a specific advantage in terms of reduced doses to normal tissues. This study investigated the fundamental differences between proton- and X-ray-induced intestinal injuries in mouse models. C57BL/6J mice were irradiated with 6-MV X-rays or 230-MeV protons and were sacrificed after 84 h. The number of surviving crypts per circumference of the jejunum was identified using Hematoxylin and Eosin staining. Diverse intestinal stem cell (ISC) populations and apoptotic cells were analyzed using immunohistochemistry (IHC) and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay, respectively. The crypt microcolony assay revealed a radiation-dose-dependent decrease in the number of regenerative crypts in the mouse jejunum; proton irradiation was more effective than X-ray irradiation with a relative biological effectiveness of 1.14. The jejunum is the most sensitive to radiations, followed by the ileum and the colon. Both types of radiation therapy decreased the number of radiosensitive, active cycling ISC populations. However, a higher number of radioresistant, reserve ISC populations and Paneth cells were eradicated by proton irradiation than X-ray irradiation, as shown in the IHC analyses. The TUNEL assay revealed that proton irradiation was more effective in enhancing apoptotic cell death than X-ray irradiation. This study conducted a detailed analysis on the effects of proton irradiation versus X-ray irradiation on intestinal crypt regeneration in mouse models. Our findings revealed that proton irradiation has a direct effect on ISC populations, which may result in an increase in the risk of GI toxicity during proton beam therapy.

NOD2 Supports Crypt Survival and Epithelial Regeneration after Radiation-Induced Injury.

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) affords stem cell protection and links microbes to intestinal epithelial regeneration. We investigated whether NOD2 status is associated with crypt survival and intestinal epithelial regeneration independent of microbiota-derived molecules. To assess crypt survival, a clonogenic microcolony assay was performed with 15 Gy of X-ray irradiation. The fractional crypt survival rate (46.0 ± 15.5% vs. 24.7 ± 9.2%, p < 0.01) and fractional EdU-positive crypt survival rate (29.8 ± 14.5% vs. 9.79 ± 4.37%, p = 0.015) were significantly decreased in the NOD2-/- mice compared with the wild-type (WT) mice at 3.5 days after irradiation. To evaluate intestinal epithelial regeneration capability, organoid reconstitution assays were performed. Small bowel crypts of the WT and NOD2-/- mice were isolated and seeded into Matrigel for 3D culture. In the organoid reconstitution assays, the number of organoids formed did not differ between the NOD2-/- and WT mice. Organoid formation ability was also assessed after exposure to 5 Gy irradiation. Organoid formation ability was significantly decreased in the NOD2-/- mice compared with the WT ones after exposure to 5 Gy irradiation (33.2 ± 5.9 vs. 19.7 ± 8.8/well, p < 0.01). NOD2 supports crypt survival after potentially lethal irradiation damage and is associated with intestinal epithelial regeneration.

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.