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.

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.

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.

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.

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.

Comparative study of Helicobacter pylori eradication rates of concomitant therapy vs modified quadruple therapy comprising proton-pump inhibitor, bismuth, amoxicillin, and metronidazole in Korea.

BACKGROUND: The standard triple Helicobacter pylori regimen now shows unacceptably low treatment success in Korea. Administration of the concomitant therapy for 10 days, which has a high cure rate, is recommended as an alternative first-line treatment in areas of high clarithromycin resistance including Korea. Recently, modified bismuth-containing quadruple therapy with amoxicillin (PAM-B therapy) showed excellent results, regardless of dual clarithromycin and metronidazole resistance. This study compared the concomitant therapy with PAM-B therapy as a first-line treatment for H. pylori infection. METHOD: Subjects infected with H. pylori and naïve to treatment were performed a head-to-head comparison between 10-day concomitant therapy [rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily] and 14-day PAM-B therapy [rabeprazole 20 mg, amoxicillin 1 g, metronidazole 750 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily]. Six weeks after treatment, H. pylori eradication was assessed. RESULTS: Two hundred and seventy subjects were randomized. Both regimens achieved high cure rates: 83.0% (112/135) and 88.1% (119/135) by the intention-to-treat analysis and 95.5% (106/111) and 96.6% (114/118) by the per-protocol analysis, respectively. The intention-to-treat and per-protocol analyses revealed no statistically significant difference in the eradication rate (P = .299 and P = .743, respectively). Rates of adverse events were similar between groups (25.2% vs 23.0%, P -value: .776) Adverse events, which resulted in poor compliance, occurred in six patients of each group, but there were no serious complications. CONCLUSIONS: PAM-B therapy is as effective as concomitant therapy for eradicating H. pylori with comparative safety. PAM-B therapy is regarded as a promising alternative to standard triple therapy for a first-line eradication in Korea.

Role of IL-1ra and Granzyme B as biomarkers in active Crohn's disease patients.

BACKGROUND AND AIM: Altered gene expression in intestinal mucosa is thought to contribute to inflammatory process in Crohn's disease (CD). The present study investigated changes in the expression of genes associated with gut inflammation in CD patients by RNA microarray to identify disease biomarkers. METHODS: Microarray analysis was carried out in formalin-fixed, paraffin-embedded intestinal tissue specimens from six CD patients who underwent surgery without prior treatment and from two healthy control subjects. Transcripts overexpressed in CD patients were validated by enzyme-linked immunosorbent assay (ELISA) using specimens from 46 CD patients and 60 healthy controls. RESULTS: Among the genes over-expressed with statistical significance, five genes including decay-accelerating factor, interleukin-1 receptor (IL1R) A, tumour necrosis factor receptor 2, (C-X-C motif) ligand (CXCL) 1, and granzyme (GZM) B proposed to have functional association with CD were selected to validate the expressed transcripts in serum. Serum concentration of IL1RA, CXCL1, and GZMB measured by ELISA were significantly higher in CD patients. CONCLUSIONS: We identified that IL1RA, CXCL1, and GZMB are overexpressed in CD patients. Serum IL1RA and GZMB levels were markedly increased in CD patients, suggesting that these markers can serve as biomarkers to identify gut inflammation. Further studies will be required to evaluate this possibility.

Helicobacter pylori eradication rates of concomitant and sequential therapies in Korea.

BACKGROUND: The efficacy of the standard triple therapy for Helicobacter pylori eradication has decreased to an unacceptable level. We aimed to compare the efficacy of sequential and concomitant therapies as for the first-line treatments for H. pylori eradication and analyzed the effect of clarithromycin resistance on the eradication rates. MATERIALS AND METHODS: Four hundred and seventy-eight patients with H. pylori infection were randomly assigned to either concomitant therapy (amoxicillin 1000 mg with clarithromycin 500 mg, metronidazole 500 mg, and pantoprazole 40 mg twice daily for 10 days) or sequential therapy (amoxicillin 1000 mg with pantoprazole 40 mg twice daily for 5 days, followed by clarithromycin 500 mg with metronidazole 500 mg and pantoprazole 40 mg twice daily for 5 days). The success of the eradication was evaluated 4-5 weeks after treatment completion. To evaluate the efficacy of the two regimens according to clarithromycin sensitivity, dual-priming oligonucleotide-based multiplex-polymerase chain reaction was also performed in the final third of the enrolled study populations. RESULTS: The eradication rates with concomitant or sequential therapy were 81.9% and 76.6% (P = .153) in intention-to-treat analysis, and 93.4% and 84.8% (P = .004) in per-protocol analysis, respectively. Among the 156 patients for whom dual-priming oligonucleotide-based multiplex-polymerase chain reaction was performed, 17.9% were clarithromycin resistant, and the efficacy of concomitant therapy was better than sequential therapy in the clarithromycin-resistant strains (100% vs 58.3%, P = .010). CONCLUSION: Concomitant therapy was superior to sequential therapy as the first-line treatment for H. pylori eradication, especially in clarithromycin-resistant strains in Korea.

Endoscopic biliary stent insertion through specialized duodenal stent for combined malignant biliary and duodenal obstruction facilitated by stent or PTBD guidance.

OBJECTIVES: Endoscopic stenting for combined malignant biliary and duodenal obstruction is technically demanding. However, this procedure can be facilitated when there is guidance from previously inserted stent or PTBD tube. This study aimed to evaluate the feasibility and clinical success rate of endoscopic placement of biliary self-expandable metal stent (SEMS) through duodenal SEMS in patients with combined biliary and duodenal obstruction due to inoperable or metastatic periampullary malignancy. MATERIALS AND METHODS: A total of 12 patients with combined malignant biliary and duodenal stricture underwent insertion of biliary SEMS through the mesh of specialized duodenal SEMS from July 2012 to October 2016. Technical and clinical success rate, adverse events and survival after completion of SEMS insertion were evaluated. RESULTS: The duodenal strictures were located in the first portion of the duodenum in four patients (Type I), in the second portion in three patients (Type II), and in the third portion in five patients (Type III). Technical success rate of combined metallic stenting was 91.7%. Insertion of biliary SEMS was guided by previously inserted biliary SEMS in nine patients, plastic stent in one patient, and PTBD in two patients. Clinical success rate was 90.9%. There were no early adverse events after the procedure. Mean survival period after combined metallic stenting was 91.9 days (range: 15-245 days). CONCLUSIONS: Endoscopic placement of biliary SEMS through duodenal SEMS is feasible with high success rates and relatively easy when there is guidance. This method can be a good alternative for palliation in patients with combined biliary and duodenal obstruction.