Gallstone Dissolution Effects of Combination Therapy with n-3 Polyunsaturated Fatty Acids and Ursodeoxycholic Acid: A Randomized, Prospective, Preliminary Clinical Trial.

Background/Aims: : Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones. Methods: : This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated. Results: : Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890). Conclusions: : UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted.

Magnetic Compression Anastomosis for the Treatment of Complete Biliary Obstruction After Cholecystectomy.

BACKGROUND & AIMS: Post-cholecystectomy biliary strictures can be treated surgically or non-surgically. Although endoscopic or percutaneous treatments are the preferred approaches, these methods are not feasible in cases where complete stricture occlusion prevents the successful passage of a guidewire. The utility of magnetic compression anastomosis (MCA) in patients with post-cholecystectomy complete biliary obstruction that cannot be treated conventionally was evaluated. METHODS: MCA was performed in 10 patients with post-cholecystectomy biliary strictures that did not resolve with conventional endoscopic or percutaneous treatment. One magnet was delivered through the percutaneous transhepatic biliary drainage tract, and another was advanced via endoscopic retrograde cholangiopancreatography(ERCP) of the common bile duct. After magnet approximation and recanalization, a fully covered self-expandable metal stent (FCSEMS) was placed for 3 months and then replaced for a further 3 months. Stricture resolution was evaluated after FCSEMS removal. RESULTS: Among the 10 patients who underwent MCA for post-cholecystectomy biliary stricture, the biliary injury was Strasberg type B in 2, type C in 3, and type E in 5. Recanalization was successful in all patients (technical success rate 100%). The mean follow-up period after recanalization was 50.2 months (range 13.2-116.8 months). Partial restenosis after MCA occurred in two patients at 24.1 and 1.6 months after stent removal. ERCP with FCSEMS placement resolved the recurrent stenosis in both patients. CONCLUSIONS: MCA is a useful alternative nonsurgical treatment for complete biliary obstruction after cholecystectomy that cannot be resolved by conventional methods.

Expression of Immunoglobulin G4 in Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is a disease that has been subcategorized into two endoscopic phenotypes: inflammatory and fibrostenotic. Moreover, studies have shown a link between EoE and immunoglobulin G4 (IgG4), a subclass of the immunoglobulin G (IgG) antibody. In this study, we aimed to evaluate the relationship between histologic IgG4 expression and endoscopic phenotypes in patients with EoE. Methods: This case-control study included patients diagnosed with EoE (n = 19) and patients with non-obstructive dysphagia without abnormal findings as controls (NOD; n = 12). The EoE group was further divided into three subgroups based on endoscopic phenotype: inflammatory, fibrostenotic, or combined. Retrospective examination of endoscopic findings and pathological slides was performed to analyze IgG4 staining. Results: Histological analysis revealed a significant difference in IgG4 cell count (15.00 vs. 0.58, p = 0.003) and eosinophil cell count (84.67 vs. 0.08, p < 0.001) between the EoE and NOD groups. Symptom manifestation and blood test results were similar across all three endoscopic EoE phenotypes. However, histological analysis revealed a significant difference in IgG4 cell count between the inflammatory, fibrostenotic, and combined phenotypes (4.13 vs. 17.6 vs. 59.7, p = 0.030). Conclusions: IgG4 expression was higher in EoE patients than in those with NOD, the highest being in the combined phenotype subgroup. These findings emphasize the important role of endoscopic and histological examination in diagnosing EoE and the need for further research in this area.

A Short Fully Covered Self-Expandable Metal Stent for Management of Benign Biliary Stricture Not Caused by Living-Donor Liver Transplantation.

Background: This study evaluated the effectiveness of short fully covered self-expanding metal stents (FCSEMS) with an anti-migration design in treating benign biliary strictures (BBS) not related to living donor liver transplantation (LDLT). Methods: A retrospective analysis was conducted on 75 patients who underwent FCSEMS insertion for BBS management. Stents were initially kept for 3 months and exchanged every 3 months until stricture resolution. Adverse events and stricture recurrence after FCSEMS removal were assessed during follow-up. Results: The study outcomes were technical success, stenosis resolution, and treatment failure. Technical success was 100%, with stricture resolution in 99% of patients. The mean onset time of BBS post-surgery was 4.4 years, with an average stent indwelling period of 5.5 months. Stricture recurrence occurred in 20% of patients, mostly approximately 18.8 months after stent removal. Early cholangitis and stent migration were noted in 3% and 4% of patients, respectively. Conclusions: This study concludes that short FCSEMS demonstrate high efficacy in the treatment of non-LDLT-related BBS, with a low incidence of interventions and complications. Although this is a single-center, retrospective study with a limited sample size, the findings provide preliminary evidence supporting the use of short FCSEMS as a primary treatment modality for BBS. To substantiate these findings, further research involving multicenter studies is recommended to provide additional validation and a broader perspective.

Triamcinolone acetonide alleviates benign biliary stricture by ameliorating biliary fibrosis and inflammation.

We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when used in conjunction with fully covered self-expandable metal stents (FCSEMS) for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohistochemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels. Overall, our findings revealed a dose-dependent decrease in fibrosisrelated signaling with higher TA concentrations. The 15 mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30 mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. Use of corticosteroids, specifically TA, together with FCSEMS was effective for the treatment of BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS as a therapeutic option for BBS in humans resulting from various surgical procedures. [BMB Reports 2024; 57(4): 200-205].

Prediction of Prognosis in Pancreatic Cancer According to Methionyl-tRNA Synthetase 1 Expression as Determined by Immunohistochemical Staining.

The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)-which facilitates cancer growth by modulating protein synthesis and the cell cycle-to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery. High MARS1 expression was defined as equal to, or greater than, that in normal acinar cells. Low MARS1 expression was defined as weaker than in normal acinar cells, and stronger than in the pancreatic duct epithelium. Univariate and multivariate analyses were performed on other factors related to prognosis. Among 137 PDAC patients, no significant differences in baseline characteristics were found between those with high (n = 82) and low (n = 55) MARS1 expression. The median overall survival time of patients with high MARS1 expression was shorter than that of those with low expression (15.2 versus 17.2 months, log-rank test p = 0.044). The median disease-free survival (DFS) was not significantly different between the two groups. However, the DFS was shorter in patients with high than in those with low MARS1 expression (8.9 versus 11.2 months, log-rank test p = 0.067). In a multivariate analysis, lymph node metastasis and high MARS1 expression were associated with a poor prognosis of PDAC. Elevated MARS1 expression detected by IHC staining is associated with a poor prognosis of PDAC, suggesting that MARS1 has potential as a prognostic marker.

Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea.

Objective: Immune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality. Methods: From the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated. Results: The adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841-0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712-0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701-0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs). Conclusion: After adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities.

Determination of chromatographic separation parameters of tryptophan enantiomers on a Chirosil-SCA chiral stationary phase by using the inverse method based on the initial guesses estimated from elution by characteristic point method.

An effective chiral stationary phase (CSP) for enantioseparation of amino acids was established previously by bonding (18-crown-6)-2, 3, 11, 12-tetracarboxylic acid to silica gel. This CSP has recently been commercialized under the name of Chirosil-SCA. As a first step for developing a Chirosil-SCA simulated moving bed chromatographic process for separation of tryptophan enantiomers, the adsorption isotherm and mass-transfer parameters of each tryptophan enantiomer on the Chirosil-SCA CSP were determined in this study while using only water as a mobile phase. For this task, inverse method (IM) was applied on the basis of the initial guesses estimated from elution by characteristic point (ECP) method, which was found to be more advantageous in the aspects of both accuracy and computational efficiency than the case of utilizing individually only IM or ECP method. The results revealed that the adsorption behavior of each tryptophan enantiomer on the Chirosil-SCA could be well described by the Langmuir-Freundlich isotherm. The model predictions based on the determined parameter values were in close agreement with the experimental chromatograms from a series of single-component or mixture pulse tests that were performed under various feed concentrations and flow rates. It was also found that the Langmuir-Freundlich isotherm parameters of each enantiomer were largely affected by temperature. Such a marked dependence of the parameters on temperature was investigated quantitatively. The results of such an investigation indicated that as the temperature decreases, the adsorption affinities of both enantiomers become higher and the heterogeneity of the Chirosil-SCA becomes more pronounced.

Continuous separation of copper ions from a mixture of heavy metal ions using a three-zone carousel process packed with metal ion-imprinted polymer.

In this study, a three-zone carousel process based on a proper molecular imprinted polymer (MIP) resin was developed for continuous separation of Cu(2+) from Mn(2+) and Co(2+). For this task, the Cu (II)-imprinted polymer (Cu-MIP) resin was synthesized first and used to pack the chromatographic columns of a three-zone carousel process. Prior to the experiment of the carousel process based on the Cu-MIP resin (MIP-carousel process), a series of single-column experiments were performed to estimate the intrinsic parameters of the three heavy metal ions and to find out the appropriate conditions of regeneration and re-equilibration. The results from these single-column experiments and the additional computer simulations were then used for determination of the operating parameters of the MIP-carousel process under consideration. Based on the determined operating parameters, the MIP-carousel experiments were carried out. It was confirmed from the experimental results that the proposed MIP-carousel process was markedly effective in separating Cu(2+) from Mn(2+) and Co(2+) in a continuous mode with high purity and a relatively small loss. Thus, the MIP-carousel process developed in this study deserves sufficient attention in materials processing industries or metal-related industries, where the selective separation of heavy metal ions with the same charge has been a major concern.