Predictive factors associated with technical difficulty in colorectal endoscopic submucosal dissection: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.

Outcomes of Colorectal Endoscopic Submucosal Dissection for Elderly Patients: A Multicenter Study by the Honam Association for the Study of Intestinal Disease (HASID).

BACKGROUND/AIM: The aging population has been growing gradually; therefore, the proportion of elderly patients undergoing colorectal endoscopic submucosal dissection (ESD) has also been increasing. However, there is a lack of large-scale studies on the efficacy and safety of colorectal ESD in elderly patients. PATIENTS AND METHODS: This retrospective analysis evaluated colorectal ESDs performed at five tertiary medical institutions between January 2015 and December 2020. Patients were categorized into the following four age groups: Middle-aged (<65 years), young-elderly (≥65 to <75 years), mid-elderly (≥75 to <85 years), and very elderly (≥85 years). Of the 1,446 patients included, 668 (46.2%), 466 (32.2%), 293 (20.3%), and 19 (1.3%) were in the middle-aged, young-elderly, mid-elderly, and very-elderly groups, respectively. RESULTS: Compared to younger patients, more older patients used aspirin, clopidogrel, and anti-thrombotic agents. Additionally, the Charlson comorbidity index increased significantly with increasing age. However, no significant differences were observed in the complete resection rates nor the rates of complications, such as perforation, bleeding, and post-ESD coagulation syndrome, among the different age groups. A restricted cubic spline curve was used to construct predictive models for complete resection and major complications based on age and showed that the need for complete resection did not decrease with increasing age. Furthermore, major complications did not significantly differ with age progression. CONCLUSION: Colorectal ESD should be actively considered as a relatively safe and effective treatment method for elderly patients.

Efficacy, tolerability, and safety of oral sulfate tablet versus 2 L-polyethylene glycol/ascorbate for bowel preparation in older patients: prospective, multicenter, investigator single-blinded, randomized study.

BACKGROUND: We compared the efficacy, tolerability, and safety of oral sulfate tablets (OST, which contains simethicone) and 2 L-polyethylene glycol/ascorbate (2 L-PEG/Asc) with a split-dosing regimen in older individuals aged ≥ 70 years who underwent scheduled colonoscopy. METHODS: This prospective, randomized, investigator-blinded, multicenter study was conducted between June 2022 and October 2023. Participants aged ≥ 70 years were randomized at a ratio of 1:1 to the OST or 2 L-PEG/Asc groups. RESULTS: In total, 254 patients were evaluated using a modified full analysis set. Successful overall bowel preparation was excellent and similar between the OST and 2 L-PEG/Asc groups for the Boston Bowel Preparation Scale (BBPS) (96.5% vs. 96.6%) and Harefield Cleansing Scale (HCS) (96.5% vs. 97.4%). The overall high-quality preparation rate was higher in the OST group than in the 2 L-PEG/Asc group (BBPS: 55.7% vs. 28.4%, P < 0.001; HCS: 66.1% vs. 38.8%, P < 0.001). The overall adenoma detection rate (54.8% vs. 35.3, P = 0.003) was superior in the OST group compared to the 2 L-PEG/Asc group. Tolerability scores, including overall satisfaction, were generally higher in the OST group than in the 2 L-PEG/Asc group. The incidence of major solicited adverse events was comparable between the two groups (55.7% vs. 68.1, P = 0.051), and there were no clinically significant changes in the serum laboratory profiles on the day of or 7 days after colonoscopy. CONCLUSIONS: OST is an effective and safe low-volume agent for colonoscopy, with better tolerance than 2 L-PEG/Asc, in older individuals aged ≥ 70 years.

Effectiveness and Safety of Endoscopic Submucosal Dissection for Colorectal Neoplasm in Patients with High Charlson Comorbidity Index Score: A HASID Multicenter Study.

Endoscopic submucosal dissection (ESD) is an effective method for removing early colorectal lesions. However, research on the safety and efficacy of ESD in patients with various underlying conditions remains limited. This study retrospectively examined ESD outcomes in colorectal neoplasm patients from five tertiary medical centers. The Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) were analyzed, and the differences in complete resection and complication rates were analyzed. The CCI, ACCI, and complication rates tended to gradually increase proportionally, and the complication resection rate increased from CCI 2 to ACCI 4 as the starting point, followed by a decreasing trend. Of these, 140 patients (9.7%) had a CCI score of 3 or higher. The high CCI group was older (70.6% vs. 64.7%, p < 0.01) and had a higher proportion of men (70.7% vs. 58.7%, p < 0.01) than the low CCI group. The high CCI group had a higher incidence of cancer than the low CCI group (77.9% vs. 65.2%, p < 0.01). The en bloc resection rate (90.0% vs. 89.3%, p = 0.79) and complete resection rate (75.7% vs. 81.2%, p = 0.12) were not significantly different between the two groups. Colorectal ESD can be safely and effectively performed in patients with various underlying medical conditions.

Comparison of optimal bowel cleansing effects of 1L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate: A randomized controlled study.

Various low-volume bowel cleansing formulations that improve compliance have been approved and are being used in clinical practice. This study aimed to compare the effectiveness of 1 L polyethylene glycol (PEG) with ascorbic acid with that of sodium picosulfate (PICO) with magnesium citrate. This was a multicenter, randomized controlled, non-inferiority study. Patients were randomized into a 1 L PEG with ascorbic acid group and a PICO with magnesium citrate group according to the bowel cleansing agent used. Colonoscopy was performed as a single-blind study wherein the endoscopist had no information about any bowel preparation agent. The efficacy of bowel cleansing was assessed using the Harefield Cleansing Scale (HCS), and adverse events, preferences, and satisfaction were evaluated using a patient-reported questionnaire before colonoscopy. A total of 254 participants were randomly assigned to two groups: 115 in the 1 L PEG with ascorbic acid group and 113 in the PICO with magnesium citrate group. Overall bowel cleansing success was not statistically different between the two groups (97.4 vs. 97.3%), confirming that 1 L PEG with ascorbic acid was not inferior to PICO with magnesium citrate (lower confidence limit, -4.15%; p = 1.00). High-quality bowel cleansing was achieved in 87% of the 1 L PEG with ascorbic acid group and 77% of the PICO with magnesium citrate group (Lower confidence limit, 1.29%, p = 0.05). In terms of patient satisfaction, PICO with magnesium citrate was better, but compliance and side effects were similar in both groups. The 1 L PEG with ascorbic acid showed similar efficacy and adverse events as PICO with magnesium citrate. Although 1 L PEG with ascorbic acid is very effective in bowel preparation despite its small volume, it is necessary to increase satisfaction such as taste and feeling.

The Common and Unique Pattern of Microbiome Profiles among Saliva, Tissue, and Stool Samples in Patients with Crohn's Disease.

This study aimed to elucidate common and unique microbiome patterns in saliva, intestinal tissue biopsy, and stool samples from patients with Crohn's disease (CD). Saliva, tissue, and stool samples from patients with CD were prospectively collected. Quantitative and phylogenetic analyses of 16s rRNA sequencing data were performed with bioinformatical pipelines. A total of 30 patients were enrolled in this study. The composition of major microbial taxa was similar between tissue and stool samples. A total of 11 of the 20 most abundant microbiota were found in both samples. The microbial community in saliva was significantly distinct from that in tissue and stool. The major species of microbiota and their composition also differed significantly from those of tissue and stool samples. However, Streptococcus and Prevotella are common genera in saliva, tissue, and stool microbiome. The abundance of Streptococcus, Pantoea, and Actinomyces from the saliva sample group were significantly different, varying with the location of the inflammation. Saliva has a distinct microbial community compared with tissues and stools in patients with CD. Prevotella and Streptococcus, which are commonly observed in saliva, stool, and tissue, can be considered a potential biomarker related to the diagnosis or prognosis of CD.

Clinical Features and Long-term Prognosis of Crohn's Disease in Korea: Results from the Prospective CONNECT Study.

Background/Aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions: The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Efficacy of sigmoidoscopy for evaluating disease activity in patients with ulcerative colitis.

BACKGROUND: Endoscopic assessment of disease activity is a key parameter in the management of ulcerative colitis. Whether sigmoidoscopy alone is sufficient to evaluate the disease activity in ulcerative colitis lacks studies. METHODS: We retrospectively analyzed the medical records and endoscopic results of patients with ulcerative colitis followed by colonoscopy in seven tertiary hospitals between January 2012 and December 2018. Endoscopic disease activity was scored using the Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for each segment from the colonoscopy images. Concordance was evaluated by comparing the highest MES and UCEIS in the rectosigmoid and proximal regions to confirm the usefulness of sigmoidoscopy. RESULTS: A total of 500 colonoscopic examinations from 333 patients were enrolled. Only in 7.6% [k(kappa): 0.893, r(Spearman): 0.906, p < 0.001] and 8.6% [k(kappa): 0.890, r(Spearman): 0.914; p < 0.001] of cases, MES and UCEIS scored more severely in the proximal colon. Comparison of active disease (MES ≥ 2) in the rectosigmoid area and the entire colon showed a high concordance rate [k(kappa): 0.899, r(Spearman): 0.904, p < 0.001]. Endoscopic healing (MES = 0) also showed a high concordance rate [k(kappa): 0.882, r(Spearman): 0.887, p < 0.001]. In 38 cases (7.6%) of patients with a higher MES in the proximal area, it was significantly higher in patients with previous extensive colitis. CONCLUSIONS: Sigmoidoscopy and colonoscopy showed a high concordance rate. Therefore, sigmoidoscopy is considered a sufficient substitute for colonoscopy. However, colonoscopy should be considered in patients with previous extensive colitis.

Development of a Clinical and Genetic Prediction Model for Early Intestinal Resection in Patients with Crohn's Disease: Results from the IMPACT Study.

Early intestinal resection in patients with Crohn's disease (CD) is necessary due to a severe and complicating disease course. Herein, we aim to predict which patients with CD need early intestinal resection within 3 years of diagnosis, according to a tree-based machine learning technique. The single-nucleotide polymorphism (SNP) genotype data for 337 CD patients recruited from 15 hospitals were typed using the Korea Biobank Array. For external validation, an additional 126 CD patients were genotyped. The predictive model was trained using the 102 candidate SNPs and seven sets of clinical information (age, sex, cigarette smoking, disease location, disease behavior, upper gastrointestinal involvement, and perianal disease) by employing a tree-based machine learning method (CatBoost). The importance of each feature was measured using the Shapley Additive Explanations (SHAP) model. The final model comprised two clinical parameters (age and disease behavior) and four SNPs (rs28785174, rs60532570, rs13056955, and rs7660164). The combined clinical-genetic model predicted early surgery more accurately than a clinical-only model in both internal (area under the receiver operating characteristic (AUROC), 0.878 vs. 0.782; n = 51; p < 0.001) and external validation (AUROC, 0.836 vs. 0.805; n = 126; p < 0.001). Identification of genetic polymorphisms and clinical features enhanced the prediction of early intestinal resection in patients with CD.

Synergistic anticancer effect of docosahexaenoic acid and isoliquiritigenin on human colorectal cancer cells through ROS-mediated regulation of the JNK and cytochrome c release.

A large body of research has demonstrated a synergistic anticancer effect between docosahexaenoic acid (DHA) and standard chemotherapy regimens against colorectal cancer (CRC). In this study, we investigated the chemotherapeutic potential of cotreatment with DHA and isoliquiritigenin (ISL) against CRC HCT-116 cells. Apoptosis was confirmed by Annexin V/PI staining and expression of apoptosis-associated proteins. The synergistic effect of DHA and ISL combination on apoptosis was detected using combination index approaches. Flow cytometry was carried out using fluorescent probes to measure the production of reactive oxygen species (ROS). DHA and ISL in combination synergistically enhanced the decrease in cell viability versus the compounds used alone. Moreover, we demonstrated that the synergistic anti-CRC activity of cotreatment with these two compounds was achieved by inducing the apoptosis caspase-dependently mediated through augmented ROS generation followed by increased Fas ligand mRNA expression and cytochrome c release. Our data also demonstrated that cotreating with DHA and ISL strongly upregulated the phosphorylation of ERK and JNK, which are functionally associated with ROS induced by the two compounds in combination. Interestingly, further study revealed that inhibiting ERK phosphorylation strongly enhanced Fas ligand mRNA expression and the combination of the two compounds induced stronger cytotoxicity, whereas inhibiting JNK phosphorylation significantly reduced the apoptotic signals mediated by cotreatment with these two compounds. Excessive ROS-induced JNK activation and cytochrome c release from mitochondria played a key role in the synergistic anticancer activity of CRC cells by cotreating with DHA and ISL.

Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study.

BACKGROUND: We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed. METHODS: Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission. RESULTS: Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event. CONCLUSIONS: Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

Risk Factors for Postoperative Recurrence in Korean Patients with Crohn's Disease.

Background/Aims: A considerable number of patients with Crohn's disease still need intestinal resection surgery. Postoperative recurrence is an important issue in Crohn's disease management, including the selection of high-risk patients. Eastern Asian patients showed several differences from Caucasian patients. Therefore, we investigated the postoperative surgical recurrence outcome and identified risk factors in Korean patients. Methods: Clinical data of 372 patients with Crohn's disease who underwent first intestinal resection between January 2004 and August 2014 at 14 hospitals in Korea were retrospectively reviewed. Results: Over the follow-up period, 50 patients (17.1%) showed surgical recurrence. The cumulative surgical recurrence rate was 6.5% at 1 year and 15.4% at 7 years. Age under 16 (p=0.011; hazard ratio [HR], 5.136; 95% confidence interval [CI], 1.576 to 16.731), colonic involvement (p=0.023; HR , 2.011; 95% CI, 1.102 to 3.670), and the presence of perianal disease at surgery (p=0.008; HR, 2.239; 95% CI, 1.236 to 4.059) were independent risk factors associated with surgical recurrence. Postoperative thiopurine treatment (p=0.002; HR, 0.393; 95% CI, 0.218 to 0.710) was a protective factor for surgical recurrence. Conclusions: Among the disease characteristics at surgery, younger age, colonic location, and perianal lesions were independent risk factors for surgical recurrence. Postoperative thiopurine treatment significantly reduced the incidence of surgical recurrence.

[Rectal Ulcer Developed in Systemic Lupus Erythematosus without Ischemic Colitis].

Rectal involvement by systemic lupus erythematosus (SLE) is quite rare. Approximately 14 cases have been reported worldwide, but only one with ischemic colitis has been reported in Korea. A 17-year-old female patient was hospitalized with abdominal pain and hematochezia. Sigmoidoscopy revealed only a simple rectal ulcer without ischemic colitis. cytomegalovirus and bacterial infections were excluded. A sigmoidoscopic rectal biopsy indicated a rectal invasion by SLE, but the patient showed an acute worsening conditions that did not respond to treatment. This paper reports a case of rectal ulcer that developed in SLE without ischemic colitis with a review of the relevant literature.

Risk factors associated with clinical outcomes of endoscopic mucosal resection for colorectal laterally spreading tumors: A Honam Association for the Study of Intestinal Diseases (HASID) multicenter study.

BACKGROUND/AIMS: Colorectal laterally spreading tumors (LSTs) are large and superficial neoplasms. Most are adenomatous lesions. Endoscopic mucosal resection (EMR) is a standard technique of removing precursor colorectal lesions. The aim of the present study was to assess the factors associated with the clinical outcomes of EMR for LSTs. MATERIALS AND METHODS: A total of 275 patients with LSTs who underwent EMR were enrolled in the study. The clinical outcomes of the patients were analyzed by retrospectively reviewing their medical records. RESULTS: The en bloc resection and R0 resection rates were 86.9% and 80.4%, respectively. The bleeding and perforation rates were 7.6% and 0.4%, respectively. The frequency of high-grade dysplasia and adenocarcinoma histology was significantly higher, and the procedure time was significantly longer in LSTs >20 mm than in those ≤20 mm. The R0 resection rate was significantly higher in LSTs ≤20 mm than in those >20 mm. The frequency of piecemeal resection was significantly higher in LSTs with an adenomatous and cancerous pit pattern than in those with a non-neoplastic pit pattern. The frequency of piecemeal resection was significantly higher in LSTs with adenocarcinoma than in those with low-grade dysplasia. Multivariate analysis revealed that adenomatous pit pattern, high-grade dysplasia, or adenocarcinoma was a significant independent risk factor of LSTs for piecemeal resection after EMR. CONCLUSION: EMR is useful for treating ≤20 mm LSTs with regard to curative resection and procedure time. LSTs with an adenomatous pit pattern, high-grade dysplasia, or adenocarcinoma are significant independent risk factors for piecemeal resection after EMR.

Clinicopathological feature and treatment outcome of patients with colorectal laterally spreading tumors treated by endoscopic submucosal dissection.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is an advanced technique that can be used to treat precancerous and early colorectal neoplasms by facilitating en bloc resection regardless of tumor size. In our study, we investigated the clinicopathological feature and the treatment outcome of patients with colorectal laterally spreading tumors (LSTs) that were treated by ESD. METHODS: The study enrolled all of 210 patients with colorectal LSTs who underwent ESD. Clinical outcomes were analyzed by retrospectively reviewing medical records. RESULTS: A cancerous pit pattern (Vi/Vn) was more common in pseudo-depressed (PD) subtype than in flat elevated (FE) subtype. The incidence of adenocarcinoma in the PD subtype and nodular mixed (NM) subtypes was significantly higher than in the homogenous (HG) subtype and FE subtype. The en bloc and R0 resection rates were 89.0% and 85.7%, respectively. The bleeding and perforation rates were 5.2% and 1.9%, respectively. The mean procedure time was much longer in the PD subtype than in the FE subtype. The en bloc resection rate was significantly higher in the NM subtype than in the HG subtype. However, there were no statistically significant differences in mean procedure time, en bloc resection rate, R0 resection rate, bleeding rate, or perforation rate between LST-granular and LST-nongranular types. CONCLUSIONS: These results indicate that ESD is acceptable for treating colorectal LSTs concerning en bloc resection, curative resection, and risk of complications. Careful consideration is required for complete resection of the PD subtype and NM subtype because of their higher malignant potential.

Clinical outcomes of endoscopic resection for colorectal laterally spreading tumors with advanced histology.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) are large, flat neoplasms that are usually treated using different endoscopic techniques based on their morphology, size, and histology. The aim of this study was to evaluate the clinical outcomes of LSTs with advanced histology treated by endoscopic resection. METHODS: A total of 246 LSTs with advanced histology [i.e., high-grade dysplasia (HGD) and adenocarcinoma (AC)] treated by endoscopic resection [i.e., endoscopic mucosal resection (EMR), EMR-precutting (EMR-P), and endoscopic submucosal dissection (ESD)] were enrolled. Clinicopathological characteristics were collected by review of patient's medical records. RESULTS: The en bloc resection and R0 resection rates were 75.6% and 85.0%, respectively. The bleeding and perforation rates were 10.2% and 2.4%, respectively. The frequency of cancerous pit pattern and bleeding was significantly higher in LSTs with AC than in LSTs with HGD. The R0 resection rate in LSTs with HGD was significantly higher than that in LSTs with AC. The frequency of cancerous pit patterns in LST cases with submucosal AC was significantly higher than those with intramucosal AC. The mean size of the LSTs was significantly larger in ESD group than in EMR or EMR-P groups. The frequencies of nodular mixed subtype, cancerous pit patterns, and en bloc resection rates were significantly higher in the ESD group than in the EMR or EMR-P groups. However, the frequency of perforation was significantly higher in EMR-P group than in EMR or ESD groups. CONCLUSIONS: These results indicate that ESD is a more acceptable treatment approach for resection of colorectal LSTs of larger size, with nodular mixed subtype, having a cancerous pit pattern or AC, using either en bloc or curative resection methods, compared to EMR or EMR-P procedures.

Risk factors for procedure-related complications after endoscopic resection of colorectal laterally spreading tumors.

Colorectal laterally spreading tumors (LSTs) are large and flat elevated neoplasms with diameters of at least 10 mm. Endoscopic resection of LSTs, with their large size and broad base, is difficult and dangerous compared with the resection of polypoid neoplasms. This study aimed to determine the risk factors for procedure-related complications including bleeding and perforation after endoscopic resection of LSTs.Patients with colorectal LST undergoing endoscopic resection at 5 university hospitals in Honam Province of South Korea were enrolled, and their records about patients, lesions, and procedure parameters associated with the occurrence of complications were reviewed retrospectively. Logistic regression analysis was performed to identify risk factors for complications.The frequency of comorbidities in bleeding group was significantly higher than in the no bleeding group. The frequency of bleeding was significantly higher in lesions with adenocarcinoma than in lesions with low or high-grade dysplasia. The frequency of bleeding was significantly higher in piecemeal resection than in en bloc resection. The frequency of perforation was significantly higher in endoscopic mucosal resection-precutting (EMR-P) than in endoscopic mucosal resection (EMR) or endoscopic submucosal dissection. The mean procedure duration was significantly longer in the perforation group than in the no perforation group. On multivariate analysis, patient comorbidity and histologic grade of the lesion were significant independent risk factors for bleeding, whereas EMR-P was a significant independent risk factor for perforation after endoscopic resection.This study demonstrated that patient comorbidity and histologic grade of lesion were significant independent risk factors for bleeding, and EMR-P was a significant independent risk factor for perforation after endoscopic resection of colorectal LSTs.

A new chalcone derivative, 3-phenyl-1-(2,4,6-tris(methoxymethoxy)phenyl)prop-2-yn-1-one), inhibits phorbol ester-induced metastatic activity of colorectal cancer cells through upregulation of heme oxygenase-1.

Chalcone (1,3-diphenyl-2-propen-1-one) derivatives exert anti-cancer activity by targeting key molecules that can lead to carcinogenesis. We synthesized the chalcone derivative 3-phenyl-1-(2,4,6-tris(methoxymethoxy)phenyl)prop-2-yn-1-one (KB-34) and previously reported its anti-inflammatory activity in macrophages. In this study, we examined the anti-metastatic activity of KB-34 against human colorectal cancer (CRC) cells and elucidated its underlying molecular mechanisms. KB-34 treatment significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration, as well as the invasion and proliferation of CRC cells (HT-29 and SW620). TPA-induced activation of NF-κB was also markedly suppressed by KB-34 in HT-29 cells. KB-34 suppressed the expression of matrix metalloproteinase-7 (MMP-7) at both the mRNA and protein levels in TPA-stimulated CRC cells (HT-29 and SW620). We also demonstrated that induced heme oxygenase-1 (HO-1) expression in CRC cells (HT-29 and SW620) and HO-1 is required for KB-34-mediated suppression of the expression of MMP-7 in TPA-stimulated HT-29 cells. Additionally, the cyclin-dependent kinase inhibitor p21 was significantly induced by treatment with KB-34 in CRC cells (HT-29 and SW620). Knockdown of HO-1 prevented the induction of p21 expression by KB-34 in HT-29 cells. Furthermore, we also demonstrated that 5-fluorouracil (5-FU) together with KB-34 produced a significantly greater inhibition of growth and stimulation of apoptosis of HT-29 cells than did 5-FU alone. In conclusion, KB-34 inhibits the TPA-stimulated metastatic potential of HT-29 cells by induction of HO-1 and may be a promising anti-cancer agent in chemotherapeutic strategies for CRC.

Ameliorative effect of Alnus japonica ethanol extract on colitis through the inhibition of inflammatory responses and attenuation of intestinal barrier disruption in vivo and in vitro.

Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract caused by high levels of pro-inflammatory cytokines and epithelial barrier dysfunction. Alnus japonica Steud. (Betulaceae) has been used in traditional Asian medicine. However, the potential of A. japonica for the treatment of intestinal inflammation has not been investigated. This study investigated the effects of ethanol extract from A. japonica bark (AJE) on colonic mucosa injury in mice with dextran sodium sulfate (DSS)-induced colitis. Treatment with AJE ameliorated pathological damage and the histopathologic features of DSS-induced colitis. The administration of AJE also inhibits DSS-induced pro-inflammatory cytokines expression, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2. Notably, AJE administration attenuated the reduction of tight junction proteins, zonula occludens (ZO)-1 and occludin, in DSS-induced colitis. In addition, AJE increased heme oxygenase (HO)-1 expression and prevented DSS-induced apoptosis in colonic epithelial cells. Furthermore, in vitro studies demonstrated that AJE inhibits TNF-α-induced IL-8, IL-1ß, and COX-2 expression in human intestinal epithelial HT-29 cells and tert-butyl hydroperoxide-induced reduction of ZO-1 and occludin expression in human intestinal epithelial Caco-2 cells. AJE-induced HO-1 protein expression was also found in both HT-29 and Caco-2 cells. Taken together, our findings demonstrated that AJE inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis in vivo and human intestinal epithelial cells in vitro. These results suggest that AJE might have beneficial effects for the treatment of IBD.

Isoliquiritigenin-mediated p62/SQSTM1 induction regulates apoptotic potential through attenuation of caspase-8 activation in colorectal cancer cells.

Isoliquiritigenin (ISL) is a natural flavonoid that exhibits anticancer properties in various carcinoma cell types. However, the precise mechanism responsible for its anticancer activity has not been elucidated fully. In the present study, we examined ISL-mediated apoptotic mechanisms in colorectal cancer (CRC) cells. ISL induced apoptosis in human HCT-116 cells and caused marked induction of p62/SQSTM1 mRNA and protein expression. Similarly, ISL potently inhibited in vivo tumor growth and induced p62/SQSTM1 expression in xenograft tumor tissues. In a p62/SQSTM1 siRNA transfection study, ISL-induced p62/SQSTM1 expression attenuated ISL-mediated apoptosis by reducing caspase-8 activation. ISL potentiated the apoptotic effects of 5-fluorouracil (5-FU) on HCT-116 cells. However, ISL-induced p62/SQSTM1 expression also attenuated the potency of apoptosis induced by the combination of 5-FU and ISL. Our results demonstrate that ISL-induced p62/SQSTM1 upregulation affects ISL-mediated apoptotic potential through attenuation of caspase-8 activation in CRC cells. These findings broaden the understanding of the molecular basis of ISL-mediated apoptosis.