Effect of Probiotics in Stress-Associated Constipation Model in Zebrafish (Danio rerio) Larvae.

The pathophysiology of functional bowel disorders is complex, involving disruptions in gut motility, visceral hypersensitivity, gut-brain-microbiota interactions, and psychosocial factors. Light pollution, as an environmental stressor, has been associated with disruptions in circadian rhythms and the aggravation of stress-related conditions. In this study, we investigated the effects of environmental stress, particularly continuous light exposure, on intestinal motility and inflammation using zebrafish larvae as a model system. We also evaluated the efficacy of probiotics, specifically Bifidobacterium longum (B. longum), at alleviating stress-induced constipation. Our results showed that continuous light exposure in zebrafish larvae increased the cortisol levels and reduced the intestinal motility, establishing a stress-induced-constipation model. We observed increased inflammatory markers and decreased intestinal neural activity in response to stress. Furthermore, the expressions of aquaporins and vasoactive intestinal peptide, crucial for regulating water transport and intestinal motility, were altered in the light-induced constipation model. Administration of probiotics, specifically B. longum, ameliorated the stress-induced constipation by reducing the cortisol levels, modulating the intestinal inflammation, and restoring the intestinal motility and neural activity. These findings highlight the potential of probiotics to modulate the gut-brain axis and alleviate stress-induced constipation. Therefore, this study provides a valuable understanding of the complex interplay among environmental stressors, gut function, and potential therapeutic strategies.

Potential Oral Microbial Markers for Differential Diagnosis of Crohn's Disease and Ulcerative Colitis Using Machine Learning Models.

Although gut microbiome dysbiosis has been associated with inflammatory bowel disease (IBD), the relationship between the oral microbiota and IBD remains poorly understood. This study aimed to identify unique microbiome patterns in saliva from IBD patients and explore potential oral microbial markers for differentiating Crohn's disease (CD) and ulcerative colitis (UC). A prospective cohort study recruited IBD patients (UC: n = 175, CD: n = 127) and healthy controls (HC: n = 100) to analyze their oral microbiota using 16S rRNA gene sequencing. Machine learning models (sparse partial least squares discriminant analysis (sPLS-DA)) were trained with the sequencing data to classify CD and UC. Taxonomic classification resulted in 4041 phylotypes using Kraken2 and the SILVA reference database. After quality filtering, 398 samples (UC: n = 175, CD: n = 124, HC: n = 99) and 2711 phylotypes were included. Alpha diversity analysis revealed significantly reduced richness in the microbiome of IBD patients compared to healthy controls. The sPLS-DA model achieved high accuracy (mean accuracy: 0.908, and AUC: 0.966) in distinguishing IBD vs. HC, as well as good accuracy (0.846) and AUC (0.923) in differentiating CD vs. UC. These findings highlight distinct oral microbiome patterns in IBD and provide insights into potential diagnostic markers.

Oral Sulfate Solution Is as Effective as Polyethylene Glycol with Ascorbic Acid in a Split Method for Bowel Preparation in Patients with Inactive Ulcerative Colitis: A Randomized, Multicenter, and Single-Blind Clinical Trial.

Background/Aims: Low-volume preparations for colonoscopy are gaining attention for their higher acceptability. However, the efficacy and safety of oral sulfate solution (OSS) preparations in patients with ulcerative colitis (UC) has not been well known. Therefore, we aimed to compare OSS and 2-L polyethylene glycol with ascorbic acid (PEG+Asc) for bowel preparation in inactive UC. Methods: A multicenter, randomized, single-blind study was conducted at six tertiary referral hospitals in Korea. Outpatients with UC who had stable disease activity were randomly allocated to the OSS group or the 2-L PEG+Asc group for bowel preparation before colonoscopy. The study outcomes included treatment efficacy, safety, tolerability, and acceptability. Bowel cleansing was assessed using the Boston Bowel Preparation Scale and rated as successful cleansing if the score was ≥6. Patient acceptance and tolerability were assessed using a 4-point ordinal scale. Additionally, disease activity and laboratory data before and after colonoscopy were evaluated to check for safety. Results: The OSS and 2-L PEG+Asc groups included 92 and 93 participants, respectively. No significant between-group difference was noted in successful cleansing (OSS [96.7%] vs 2-L PEG+Asc [97.8%], p=0.64). Moreover, the safety, acceptance, and tolerability were not significantly different (all p>0.05). Furthermore, no significant changes were found in serum electrolytes or disease activity in either group. Conclusions: OSS is effective for colonoscopy cleansing, has acceptable tolerability, and does not affect disease activity; thus, it can be used safely for bowel preparation in patients with inactive UC.

The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice.

Uncontrolled chronic inflammation and necrosis is characteristic of inflammatory bowel disease (IBD). This study aimed to investigate the effect of necrosis inhibitor (NI, NecroX-7) on a dextran sulfate sodium (DSS) induced chronic colitis model of mice. DSS was administered on days 1-5, and the NI was administered intraperitoneally (3 mg/kg, 30 mg/kg) on days 1, 3, and 5 as well as every other day during the first five days of a three-week cycle. Three cycles of administration were performed. Colitis was evaluated based on the disease activity index (DAI) score, colon length, and histological score. Reverse transcription polymerase chain reaction testing, the Western blot assay, and immunohistochemical staining were performed to determine inflammatory cytokine levels. The NI reduced body weight change and the DAI score. Colon length and the histological score were longer and lower in the NI-treated groups, respectively. The NI decreased the expression of pro-inflammatory cytokines, particularly in tumor necrosis factor alpha (TNF-α) and phosphorylated nuclear factor kappa B (p-NF-κB). Immunohistochemical staining revealed decreased inducible nitric oxide synthase (iNOS) and high mobility group box 1 (HMGB1) levels. Overall, the NI improved DSS induced chronic colitis by attenuating the mRNA expression of pro-inflammatory cytokines such as TNF-α. Therefore, NI use is a potential, novel treatment approach for IBD.

Comparison of the Pharmacokinetics of CT-P13 Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.

A Machine Learning-Based Diagnostic Model for Crohn's Disease and Ulcerative Colitis Utilizing Fecal Microbiome Analysis.

Recent research has demonstrated the potential of fecal microbiome analysis using machine learning (ML) in the diagnosis of inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC). This study employed the sparse partial least squares discriminant analysis (sPLS-DA) ML technique to develop a robust prediction model for distinguishing among CD, UC, and healthy controls (HCs) based on fecal microbiome data. Using data from multicenter cohorts, we conducted 16S rRNA gene sequencing of fecal samples from patients with CD (n = 671) and UC (n = 114) while forming an HC cohort of 1462 individuals from the Kangbuk Samsung Hospital Healthcare Screening Center. A streamlined pipeline based on HmmUFOTU was used. After a series of filtering steps, 1517 phylotypes and 1846 samples were retained for subsequent analysis. After 100 rounds of downsampling with age, sex, and sample size matching, and division into training and test sets, we constructed two binary prediction models to distinguish between IBD and HC and CD and UC using the training set. The binary prediction models exhibited high accuracy and area under the curve (for differentiating IBD from HC (mean accuracy, 0.950; AUC, 0.992) and CD from UC (mean accuracy, 0.945; AUC, 0.988)), respectively, in the test set. This study underscores the diagnostic potential of an ML model based on sPLS-DA, utilizing fecal microbiome analysis, highlighting its ability to differentiate between IBD and HC and distinguish CD from UC.

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.

Ten-year trends of utilizing palliative care and palliative procedures in patients with gastric Cancer in the United States from 2009 to 2018 - a nationwide database study.

OBJECTIVES: Little is known about the current status and the changing trends of hospitalization and palliative care consultation of patients with gastric cancer in the United States. The aim of this study was to evaluate the changing trend in the number of hospitalization, palliative care consultation, and palliative procedures in the US during a recent 10-year period using a nationwide database. METHODS: This was a retrospective study that analyzed the National Inpatient Sample (NIS) database of 2009-2018. Patients aged more than 18 years who were diagnosed with a gastric cancer using International Classification of Diseases (ICD)-9 and 10 codes were included. Palliative care consultation included palliative care (ICD-9, V66.7; ICD-10, Z51.5) and advanced care planning (ICD-9, V69.89; ICD-10, Z71.89). Palliative procedures included percutaneous or endoscopic bypass, gastrostomy or enterostomy, dilation, drainage, nutrition, and irrigation for palliative purpose. RESULTS AND DISCUSSION: A total of 86,430 patients were selected and analyzed in this study. Using a compound annual growth rate (CAGR) approach, the annual number of hospitalizations of gastric cancer patients was found to be decreased during 2009-2018 (CAGR: -0.8%, P = 0.0084), while utilization rates of palliative care and palliative procedures increased (CAGR: 9.3 and 1.6%, respectively; P < 0.0001). Multivariable regression analysis revealed that palliative care consultation was associated with reduced total hospital charges (-$34,188, P < 0.0001). CONCLUSION: Utilization of palliative care consultation to patients with gastric cancer may reduce use of medical resources and hospital costs.

Efficacy and Safety of TJP-008 Compared to 2 L PEG with Ascorbate in Colon Cleansing: A Randomized Phase 3 Trial.

BACKGROUND/AIMS: Polyethylene glycol (PEG)-based bowel preparations are effective cleansing agents for colonoscopy. However, they require relatively large volumes to be used even with agents such as 2 L PEG with ascorbate (2LPEG). This phase 3, randomized, single-blinded, multicenter, parallel-group study compared the efficacy of 1 L PEG with high-dose ascorbate, TJP-008, to 2LPEG. METHODS: Patients undergoing colonoscopy were randomized (1:1:1) to receive TJP-008 as 1-day split dose (TJP-008-1) or 2-day split dose (TJP-008-2) regimen or to receive 2LPEG as a 2-day split dose regimen. Cleansing efficacy was evaluated using the Harefield Cleansing Scale. The primary endpoint was overall bowel cleansing success. Full analysis set (FAS) and per protocol set (PPS) analyses were performed. RESULTS: Of the 314 screened patients, efficacy was assessed in the following patient numbers (FAS/PPS): total (293/285), TJP-008-1 (98/94), TJP-008-2 (97/95), and 2LPEG (98/96). FAS revealed noninferiority between TJP-008 and 2LPEG with regard to overall success (TJP-008-2, 99.0%; TJP-008-1, 95.9%; 2LPEG, 94.9%; p=0.100 and p=0.733, respectively). PPS also showed noninferiority (p=0.721 and p=0.211, respectively). However, the PPS analyses showed a higher bowel cleansing score for TJP-008-2 for high-quality cleansing in the right colon (TJP-008-2 83.2% vs 2LPEG 62.5%; p=0.005). CONCLUSIONS: TJP-008 is a new low-volume cleansing agent with a colon cleansing efficacy comparable to that of standard 2LPEG that exhibits significant safety and tolerability.

Prokinetic effects of diatrizoate meglumine (Gastrografin®) in a zebrafish for opioid-induced constipation model.

Constipation is a common disease that reduces life quality. Drugs of various mechanisms are being developed to resolve this affliction. Intestinal motility can be easily monitored in zebrafish, and so we selected this organism to develop a constipation model to measure drug-induced prokinetic effects. In this study, intestinal motility was monitored in zebrafish by tracking intestinal transit using fluorescence, after which an opioid-induced constipation model was established using loperamide. We then evaluated the prokinetic effect of diatrizoate meglumine (Gastrografin®), which has been empirically used to treat post-operative ileus or adhesive small bowel obstructions. Diatrizoate meglumine was effective in promoting bowel movements in an opioid-induced zebrafish constipation model and its prokinetic effect was associated with an increased expression of interstitial cells of Cajal (ICC) markers. Therefore, the loperamide-induced zebrafish constipation model developed herein is a promising tool to evaluate novel constipation therapies.

Palliative Care and Life-Sustaining/Local Procedures in Colorectal Cancer in the United States Hospitals: A Ten-Year Perspective.

BACKGROUND: In recent years, palliative care utilization has been increasing while life-sustaining/local procedures have been declining at the end of life. Palliative care utilization widely varies based on tumor type. Limited information is available on inpatient palliative care in colorectal cancer. AIMS: This study investigated inpatient palliative care utilization and its association with patient demographics, hospital charges, and procedures among colorectal cancer patients admitted to US hospitals between 2008 and 2017. Receipt of life-sustaining and local procedures and surgeries were also investigated during the ten years. METHODS: Data were extracted from the National inpatient sample (NIS) database containing de-identified information from each hospitalization. Codes V66.7 for ICD-9-CM or Z51.5 for ICD-10-CM were used to find palliative care utilization. Data were analyzed using generalized regression with adjustment for variations in predictors. The Compound Annual Growth Rate (CAGR) was calculated for palliative care and procedures over time. RESULTS: Of the 487,027 colorectal cancer hospitalizations, only 6.04% utilized palliative care. This percentage significantly increased over time from 2.3% in 2008 to 9.3% in 2017 (P<0.0001). Palliative care utilization sizably decreased hospital charges by $18,010 per hospitalization (P<0.0001) and was positively associated with female gender, severe disease, and age over 80 years (P≤ 0.05). Palliative care utilization was inversely associated with using life-sustaining and local procedures and surgeries (P<0.0001). Life-sustaining procedures (intubation, infusion of concentrate nutrients, dialysis, and blood transfusion) and surgeries were decreased over time (P<0.001). CONCLUSIONS: Palliative care utilization increased over time and was inversely associated with hospital charges and performing procedures among colorectal cancer patients. Our findings warrant further research and interventions to increase palliative care utilization in colorectal cancer.

Primary prophylaxis of gastric variceal bleeding: endoscopic obturation, radiologic intervention, or observation?

BACKGROUND: No single effective method has yet been established for the primary prophylaxis of bleeding from gastric varices (GV). METHODS: We retrospectively analyzed liver cirrhosis patients with GV who had undergone either endoscopic variceal obturation (EVO) or balloon-occluded retrograde transvenous obliteration (BRTO) as prophylactic treatments, comparing them with those who were observed without any procedural intervention. The endpoints were GV bleeding rate and complete eradication rate. RESULTS: 72 patients in EVO, 41 patients in BRTO, and 97 patients in the clinical observation groups were enrolled. No difference was observed in baseline characteristics. As the primary endpoint, 14 (19.4%) patients in the EVO group and 3 (7.3%) in the BRTO group bled from GV after prophylactic treatment, and 34 (35.1%) patients bled in the observation group during the median follow-up of 35 months (p = 0.001). Patients who received EVO or BRTO developed less bleeding from GV than those who received observation only, with no difference between EVO and BRTO (EVO vs. observation, p = 0.038; BRTO vs. observation, p = 0.001; EVO vs. BRTO, p = 0.089). As secondary endpoints, GV disappeared completely in 33 patients (45.8%) in the EVO group and 31 patients (75.6%) in the BRTO group (p = 0.003). By multivariate analysis, complete eradication of GV was the sole determinant for predicting GV bleeding. CONCLUSIONS: EVO and BRTO are effective and safe primary prophylactic treatments for preventing bleeding from GV. In particular, BRTO is better than EVO in complete eradication of GV.

A case report of a patient presented with skin ulcer after treatment of lenvatinib.

A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.

Enteroscopy in Crohn's Disease: Are There Any Changes in Role or Outcomes Over Time? A KASID Multicenter Study.

Background/Aims: Although balloon-assisted enteroscopy (BAE) enables endoscopic visualization of small bowel (SB) involvement in Crohn's disease (CD), there is no data on the changes in outcomes over time. We therefore investigated the changes in BAE use on CD patients over different time periods in terms of its role and clinical outcomes. Methods: We used a multicenter enteroscopy database to identify CD patients with SB involvement who underwent BAE (131 procedures, 116 patients). We compared BAE-related factors and outcomes between the first period (70 procedures, 60 patients) and the second period (61 procedures, 56 patients). The specific cutoff point for dividing the two periods was 2007, when BAE guidelines were introduced. Results: Initial diagnosis of SB involvement in CD was the most common indication for BAE during each period (50.0% vs 31.1%, p=0.034). The largest change was in the number of BAE uses for stricture evaluation and/or treatment, which increased significantly in the latter period (2.9% vs 21.3%, p=0.002). The diagnostic yield in patients with suspected CD was 90.7% in the first period and 95.0% in the second (p=0.695). More endoscopic interventions were performed in the second period than in the first (5.1% vs 17.6%, p=0.041). Enteroscopic success rates were high throughout (100% in the first period vs 80.0% in the second period, p>0.999). In the first and second periods, therapeutic plans were adjusted in 62.7% and 61.4% of patients, respectively. Conclusions: The overall clinical indications, outcomes, and effectiveness of BAE were constant over time in CD patients with SB involvement, with the exception that the frequency of enteroscopic intervention increased remarkably.

Incidence and risk factors for postoperative common bile duct stones in patients undergoing endoscopic extraction and subsequent cholecystectomy.

BACKGROUND AND AIMS: In patients who undergo cholecystectomy after endoscopic common bile duct (CBD) stone extraction, CBD stones found postoperatively could be problematic. This study aimed to investigate the incidence and risk factors of postoperative CBD stones after cholecystectomy. METHODS: A total of 278 patients (mean age, 59.2 years; 71 men [51.1%]) who underwent endoscopic removal of CBD stones followed by cholecystectomy from January 2013 to December 2017 were included. An endoscopic nasobiliary drainage (ENBD) tube was placed immediately after endoscopic clearance of the CBD stones in all patients until cholecystectomy. An ENBD tubogram was obtained in all patients to determine the presence of postoperative CBD stones. RESULTS: Postoperative CBD stones were detected in 20.1% (56/278). An ENBD tubogram was obtained after an average of 2.42 days postoperatively. Based on univariate analysis, the statistically significant risk factors for postoperative CBD stone were CBD stones >2, CBD stone size >10 mm, cholesterol stone, maximum diameter of CBD >15 mm, treatment with endoscopic sphincterotomy alone, and use of endoscopic mechanical lithotripsy (EML). In multivariate analysis, cholesterol stone, CBD stones >2, CBD stone size >10 mm, and EML were related to postoperative CBD stones after cholecystectomy. CONCLUSIONS: Based on the relatively high rate of postoperative CBD stones after cholecystectomy, careful follow-up should be considered in patients with high-risk factors to detect CBD stones early.

Efficacy of Low Dose Proton Pump Inhibitor-Based Therapy to Eradicate Helicobacter pylori in Patients with Subtotal Gastrectomy.

Proton pump inhibitor (PPI)-based therapy is standard to eradicate Helicobacter pylori (H. pylori). Gastric acidity is lowered after gastrectomy because of bile reflux and impaired mechanism of acid secretion. Therefore, low-dose PPI may be effective for H. pylori eradication in the remnant stomach after gastrectomy. In this study, we compared the efficacy of low-dose PPI with standard double-dose PPI to eradicate H. pylori in patients who underwent subtotal gastrectomy. A total of 145 patients who were treated for eradication after gastrectomy was analyzed. They were treated with PPI-based triple regimen (PPI, clarithromycin and amoxicillin) for 14 days. We compared the eradication rate in the low-dose PPI group (lansoprazole 15 mg once daily) with that in the standard double-dose PPI group (lansoprazole 30 mg twice daily). The H. pylori eradication rate was 79.1% in the low-dose PPI group and 85.3% in the standard double-dose group; the difference was not significant statistically (p = 0.357). In the multivariate analysis, low-dose PPI (odds ratio (OR) = 1.79, 95% confidence interval (CI), 0.68-4.69) was not associated with eradication failure, while Billroth II anastomosis (OR = 4.45, 85% CI, 1.23-16.2) was significantly associated with eradication failure. Low-dose PPI-based triple regimen was as effective as standard double-dose PPI-based regimen for H. pylori eradication in patients with subtotal gastrectomy. Further study is needed to confirm the effect of low-dose PPI on H. pylori eradication in patients with gastrectomy.

High-Definition Chromoendoscopy Versus High-Definition White Light Colonoscopy for Neoplasia Surveillance in Ulcerative Colitis: A Randomized Controlled Trial.

OBJECTIVES: Although chromoendoscopy is currently the recommended mode of surveillance in patients with long-standing ulcerative colitis, it is technically challenging and requires a long procedure time. The aim of this study was to compare the dysplasia detection rate of high-definition white light endoscopy with random biopsy (HDWL-R) vs high-definition chromoendoscopy with targeted biopsy (HDCE-T). METHODS: This was a multicenter, prospective randomized controlled trial involving 9 tertiary teaching hospitals in South Korea. A total of 210 patients with long-standing ulcerative colitis were randomized to undergo either the HDWL-R group (n = 102) or HDCE-T group (n = 108). The detection rates of colitis-associated dysplasia (CAD) or all colorectal neoplasia from each trial arm were compared. RESULTS: There was no significant difference in the CAD detection rate between HDCE-T and HDWL-R groups (4/102, 3.9% vs 6/108, 5.6%, P = 0.749). However, HDCE-T showed a trend toward improved colorectal neoplasia detection compared with HDWL-R (21/102, 20.6% vs 13/108, 12.0%, P = 0.093). The median (range) time for colonoscopy withdrawal between the 2 groups was similar (17.6 [7.0-43.3] minutes vs 16.5 [6.3-38.1] minutes; P=0.212; for HDWL-R and HDCE-T, respectively). The total number of biopsies was significantly larger in the HDWL-R group (34 [12-72]) compared with the HDCE-T group (9 [1-20]; P < 0.001). DISCUSSION: On the basis of our prospective randomized controlled trial, HDCE-T was not superior to HDWL-R for detecting CADs.

Prognostic assessment using a new substaging system for Barcelona clinic liver cancer stage C hepatocellular carcinoma: A nationwide study.

AIM & BACKGROUND: Advanced hepatocellular carcinoma (HCC) (Barcelona clinic liver cancer [BCLC] stage C) needs subclassification to more accurately predict survival. This study aims to establish a substaging system of BCLC stage C HCC patients for accurate prognosis. METHODS: Data from 564 patients with newly diagnosed BCLC stage C HCC from three tertiary-care hospitals affiliated with the Korea University (training set) were assessed retrospectively. Variables affecting overall survival (OS) were analysed, and patients were substaged according to the number of prognostic factors they fulfilled. The substaging system was validated using a nationwide database from the Korean Liver Cancer Association (validation set; n = 742). RESULTS: In the training set, tumour factors such as tumour burden ≥10 cm, major portal vein invasion and distant metastasis, as well as underlying liver function, were independently associated with OS. BCLC stage C was classified into four substages (C1-4) according to the number of prognostic factors. Substages C1, C2, C3 and C4 showed a median OS of 17.50 months (95% confidence interval [CI], 8.57-26.43), 10.13 months (95% CI, 8.17-12.09), 4.20 months (95% CI, 3.42-4.98), and 2.90 months (95% CI, 2.34-3.46) respectively (P < 0.05). This substaging system also had good discriminative ability in predicting survival in the validation set. In addition, it was considered that the BCLC substaging is better than Hong Kong liver cancer substaging in predicting the OS for patients with advanced HCC. CONCLUSION: Our substaging for BCLC stage C might help predict patients' prognosis better.

Two-year delay in ulcerative colitis diagnosis is associated with anti-tumor necrosis factor alpha use.

BACKGROUND: Ulcerative colitis (UC) is an uncommon inflammatory bowel disease (IBD). However, its incidence has recently increased in South Korea. Moreover, UC diagnoses are frequently delayed, and the relationship between diagnostic delay and UC prognosis has not been extensively studied in South Korean patients. AIM: To identify meaningful diagnostic delay affecting UC prognosis and to evaluate risk factors associated with diagnostic delay in South Korean patients. METHODS: Medical records of 718 patients with UC who visited the outpatient clinic of six university hospitals in South Korea were reviewed; 167 cases were excluded because the first symptom date was unknown. We evaluated the relationship between the prognosis and a diagnostic delay of 3, 6, 12, 18, and 24 mo by comparing the prognostic factors [anti-tumor necrosis factor (TNF)-α use, admission history due to acute flare-ups, frequent admission due to flare-ups, surgery associated with UC, and the clinical remission state at the latest follow-up] at each diagnostic interval. RESULTS: The mean diagnostic interval was 223.3 ± 483.2 d (median, 69 d; 75th percentile, 195 d). Among the prognostic factors, anti-TNFα use was significantly increased after a diagnostic delay of 24 mo. Clinical risk factors predictive of a 24-mo diagnostic delay were age < 60 years at diagnosis [odd ratio (OR) = 14.778, 95% confidence interval (CI): 1.731-126.121], smoking history (OR = 2.688, 95%CI: 1.239-5.747, P = 0.012), and misdiagnosis of hemorrhoids (OR = 11.066, 95%CI: 3.596-34.053). Anti-TNFα use was associated with extensive UC at diagnosis (OR = 3.768, 95%CI: 1.860-7.632) and 24-mo diagnostic delay (OR = 2.599, 95%CI: 1.006-4.916). CONCLUSION: A diagnostic delay > 24 mo was associated with increased anti-TNFα use. Age < 60 years at diagnosis, smoking history, and misdiagnosis of hemorrhoids were risk factors for delayed diagnosis.