Gut and Liver最新文献

Background/aims: The relationship between Helicobacter pylori (HP) eradication and osteoporosis development remains inadequately elucidated. This study aimed to ascertain whether HP eradication therapy confers protective effects against osteoporosis progression.

Methods: Subjects without osteoporosis who underwent esophagogastroduodenoscopy with concurrent HP testing were prospectively recruited between May 2003 and February 2023 at Seoul National University Bundang Hospital. Participants were stratified into two cohorts: those with successful HP eradication and those without. Osteoporosis was diagnosed using dual-energy X-ray absorptiometry, and the risk of osteoporosis was assessed using Cox proportional hazards regression analysis.

Results: The successfully eradicated cohort comprised 730 individuals (mean age, 56.4 years; 67.5% female), compared with 116 individuals (mean age, 56.2 years; 74.1% female) in the non-eradicated cohort. Osteoporosis occurred in 179 subjects (24.5%) in the eradicated group and in 40 subjects (34.5%) in the non-eradicated group. Significant risk factors for osteoporosis included female sex (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.93 to 5.05; p<0.001), advanced age (HR, 1.08; 95% CI, 1.06 to 1.10 per year; p<0.001), and persistent HP infection (HR, 1.60; 95% CI, 1.13 to 2.28; p=0.009). In subgroup analyses according to sex and age, HP eradication demonstrated a significant reduction in osteoporosis risk in females (p=0.005) than in males, especially among females aged ≥50 years (p=0.003). However, this change was not pronounced in males.

Conclusions: HP eradication may serve as a preventive intervention against osteoporosis development, particularly among female subjects (ClinicalTrials.gov: NCT06818591).

Background/aims: Studies have demonstrated that gastroesophageal reflux disease has an unfavorable effect on sleep. However, it is largely unknown whether erosive esophagitis (EE) is associated with sleep issues.

Methods: Study participants were 335,883 Korean adults who underwent upper endoscopy and completed the Pittsburgh Sleep Quality Index (PSQI) as part of a health check-up. Study participants were divided into an EE group and a non-EE group. Multivariable adjusted logistic regression analysis was used in calculating the odds ratio (OR) and 95% confidence interval (CI) (adjusted OR [95% CI]) for poor sleep quality, long sleep induction time, interrupted sleep, sleep pill use, and short sleep duration in the two groups. Subgroup analysis was conducted after stratifying the EE group patients on the basis of the extent of EE (Los Angeles classification [LA]-A, LA-B/C/D).

Results: While the prevalence of EE was higher in men (11.1%) than women (1.8%), the mean PSQI score was higher in women (5.3±2.7) than in men (4.9±2.3). In men, EE was associated with poor sleep quality (adjusted OR, 1.04; 95% CI, 1.01 to 1.08), long sleep induction time (adjusted OR, 1.10; 95% CI, 1.03 to 1.18), and interrupted sleep (adjusted OR, 1.11; 95% CI, 1.04 to 1.19). Subgroup analysis showed that LA-A was significantly associated with poor sleep quality (adjusted OR, 1.04; 95% CI, 1.01 to 1.08), long sleep induction time (adjusted OR, 1.11; 95% CI, 1.03 to 1.19), and interrupted sleep (adjusted OR, 1.12; 95% CI, 1.04 to 1.20) in men. In contrast, women failed to show a significant association between EE and sleep issues.

Conclusions: EE was associated with a modest increase in the likelihood of poor sleep quality, long sleep induction time, and interrupted sleep among men.

Background/aims: The efficacy of proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) in the treatment of eosinophilic esophagitis (EoE) has been well established. This study aimed to clarify the impact of PPIs/P-CABs on esophageal wall thickness and clinical symptoms in EoE patients.

Methods: Patients who were consecutively diagnosed with asymptomatic esophageal eosinophilia and EoE and treated with PPIs/P-CABs were assessed in this study. Esophageal wall thickness before and after treatment was evaluated using endoscopic ultrasonography.

Results: Thirteen patients were asymptomatic, while 20 presented with gastrointestinal symptoms at baseline. Treatment led to significant decreases in symptom scores, the EoE Endoscopic Reference Scores, and the EoE Histologic System Scores compared with those at baseline. Following treatment, significant reductions were observed in the total esophageal wall thickness (TWT) and thickness from the surface to the muscular layer (TSM) across the upper, middle, and lower esophagus compared with baseline values (median TWT, 2.0 mm vs 1.7 mm, p=0.005; 2.3 mm vs 1.9 mm, p=0.004; 2.9 mm vs 2.3 mm, p<0.001; median TSM, 1.1 mm vs 0.9 mm, p=0.001; 1.3 mm vs 1.1 mm, p<0.001; 1.8 mm vs 1.4 mm, p<0.001, respectively). Similar trends were observed in the lower esophagus of patients with asymptomatic esophageal eosinophilia, with the TWT and TSM values significantly lower after treatment (median TWT, 2.7 mm vs 2.5 mm, p=0.045; median TSM, 1.7 mm vs 1.5 mm, p=0.008, respectively). These findings were consistent in patients treated with either PPIs (p=0.027 and p=0.018, respectively) or P-CABs (p<0.001 and p<0.001, respectively).

Conclusions: PPIs/P-CABs reduce esophageal wall thickening, particularly in the mucosal and submucosal layers.

Background/aims: Silymarin has been reported to be hepatoprotective and to improve liver function; however, its clinical effectiveness in specific liver diseases remains unclear. This study aimed to evaluate the impact of Legalon, which contains silymarin as its active ingredient, on changes in liver function test values and to assess its potential use as a practical treatment option for liver diseases.

Methods: This multicenter retrospective cohort study used the Common Data Model. Data were collected from adult patients with liver disease who were first prescribed Legalon between January 1, 2013, and December 31, 2022, across 10 medical institutions in South Korea. Changes in liver function test values at follow-up time points were compared with baseline values.

Results: Patients who were prescribed Legalon for at least 6 months showed a statistically significant decrease in liver function test values (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) compared with baseline values. At 3 and 6 months, aspartate aminotransferase decreased by approximately 23.18% and 24.54%, alanine aminotransferase decreased by 20.24% and 25.12%, and alkaline phosphatase decreased by 3.02% and 5.90%, respectively. All three parameters showed a sustained decline.

Conclusions: Our findings indicate that silymarin (Legalon) induces a significant reduction in liver function test values, thus suggesting that this drug exerts medium to long-term hepatoprotective benefits. Moreover, the synergistic effects of silymarin with standard treatments highlight its potential as a complementary therapy for liver diseases.

Background/aims: Pancreatic ductal adenocarcinoma (PDAC) is a challenging cancer to treat and has a poor prognosis and limited treatment options. In this study, the anticancer effects of disulfiram combined with copper (DSF/Cu) on PDAC cells, including those resistant to 5-fluorouracil, was assessed.

Methods: Human pancreatic cancer cells (BxPC-3 and CFPAC-1) and their 5-fluorouracil-resistant (5FUR) counterparts were treated with DSF/Cu to assess cytotoxicity. Expression levels of nuclear factor E2-related factor-2 (NRF-2) and heme oxygenase-1 (HO-1) were analyzed by reverse transcription quantitative polymerase chain reaction and Western blotting, while intracellular reactive oxygen species (ROS) levels were evaluated using H2DCFDA staining and flow cytometry. The effects of DSF/Cu on protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways were evaluated by Western blot analysis. In vivo efficacy was investigated using a xenograft mouse model, in which mice were orally administered DSF (75 mg/kg) and Cu (2 mg/kg) twice weekly for 5 weeks.

Results: We demonstrated that DSF/Cu effectively induced cytotoxicity in both pancreatic cancer cells and their 5FUR counterparts by modulating ROS levels, NRF-2 levels, and associated survival pathways. DSF/Cu treatment significantly decreased NRF-2 expression and reduced ROS levels, specifically in 5FUR cells. DSF/Cu facilitated NRF-2-independent HO-1 expression and differentially modulated Akt and MAPK signaling pathways in pancreatic cancer cells and their 5FUR counterparts. In vivo studies using a xenograft mouse model confirmed the antitumor efficacy of DSF/Cu, as evidenced by reduced tumor volumes and NRF-2 expression.

Conclusions: These findings highlight the potential of DSF/Cu as a novel and effective therapeutic strategy for PDAC, specifically for overcoming resistance to standard therapies.

Background/aims: To construct a new model based on folate receptor-positive circulating tumor cells (FR⁺-CTC) for the preoperative prediction of peritoneal metastasis in gastrointestinal malignancies and to apply this model in clinical practice.

Methods: Patients with gastrointestinal malignancies who had undergone preoperative FR⁺-CTC counts were retrospectively collected. Risk factors for peritoneal metastasis in patients with gastrointestinal malignancies were identified using a logistic regression model. The "pROC" package in R software was employed to plot the receiver operating characteristic curve for predicting peritoneal metastasis in these patients based on identified risk factors. Spearman correlation analysis was performed to assess the relationship between FR⁺-CTC counts and risk factors.

Results: A total of 396 patients meeting the inclusion criteria were finally included in the study. The number of FR⁺-CTC, albumin level, total protein level, and cancer antigen 125 (CA-125) level were identified as risk factors affecting peritoneal metastasis in gastrointestinal malignancies. The number of FR⁺-CTC was significantly negatively correlated with albumin (R=-0.21, p<0.001), and total protein levels (R=-0.10, p=0.047), and a positively correlated with CA-125 level (R=0.15, p=0.004). The number of FR⁺-CTCs was significantly higher in patients with peritoneal metastasis, lymph node metastasis, vascular invasion, neural invasion, and in those with stage T3-4 and III-IV gastrointestinal malignancies (p<0.05 for all). The model demonstrated stable predictive capacity, as validated through 10-fold cross-validation.

Conclusions: FR⁺-CTCs can serve as a novel biomarker for gastrointestinal malignancies. A new model based on FR⁺-CTCs demonstrated strong predictive capabilities for the preoperative assessment of peritoneal metastasis in gastrointestinal cancers.

Background/aims: Gastrointestinal amyloidosis (GIA) is a common condition that presents with a variety of endoscopic features. However, the classification of these endoscopic features of GIA and its clinical implications have not been investigated.

Methods: The endoscopic findings of 127 patients with GIA were reviewed and classified by three experienced endoscopists. The relationships of the endoscopic classification of GIA with clinical amyloidosis entities, symptoms, and patient outcomes were evaluated.

Results: Five distinct types of endoscopic lesion features were identified in GIA patients: protruding, granular, hemorrhagic, ulcerative, and nonspecific. The hemorrhagic type was most common (n=32, 25.2%), followed the by protruding (n=30, 23.6%), ulcerative (n=28, 22.0%), granular (n=20, 15.7%), and nonspecific types (n=17, 13.4%). The protruding type was significantly prevalent in patients with localized amyloidosis (23/49, 71.4%), whereas the hemorrhagic type was the most common in patients with immunoglobulin light chain amyloidosis (20/47, 42.6%), and the ulcerative type was the most common in patients with amyloid A amyloidosis (8/17, 47.1%) (p<0.001). The granular type was related to dysmotility symptoms (p=0.018). Among 30 GIA patients with the protruding type, two died, whereas 36.1% of patients with the other endoscopic types (35/97) died during a median follow-up of 95.5 months (interquartile range, 65.8 to 132.0 months) (p=0.007).

Conclusions: Five types of GIA lesions were identified, and on this basis, an endoscopic classification system was proposed. This system may be of diagnostic and prognostic value.

Background/aims: The presence of individual cancer cells at the invasive tumor front is referred to as tumor budding (TB). The purpose of this study was to assess the clinicopathological significance of TB in patients with early gastric cancer (EGC).

Methods: A total of 939 patients who received radical surgery for EGC were included in this retrospective study. We assessed clinicopathological features in relation to TB including the grade of histologic differentiation, the extent of invasion depth, the width of submucosal (SM) invasion, and the presence of lymphovascular invasion (LVI), lymph node metastasis (LNM) and perineural invasion (PNI).

Results: TB was identified in 59.5% of the patients with EGC, 38.7% of the patients with mucosal invasive cancer, and 80.4% of the patients with SM invasive cancers. TB showed significant association with male sex, undifferentiated tumor types, SM invasion, LVI, PNI, and LNM. The presence of SM invasion (odds ratio [OR], 8.750; p<0.001), TB (OR, 5.586; p<0.001), and an undifferentiated-type histology (OR, 2.648; p=0.0005) were found to be significantly associated with LNM/LVI. TB was the sole significant risk factor for LNM/LVI (OR, 7.181; p=0.0016) among the mucosal invasive cancers. In SM invasive cancers, three independent risk factors for LNM/LVI were identified: a tumor located in the lower third of the stomach (OR, 3.425; p=0.0061), an undifferentiated-type histology (OR, 2.320; p=0.0177), and an SM invasion width greater than 4,000 μm (OR, 2.849; p=0.0041).

Conclusions: TB may be an important factor associated with LNM, particularly in mucosal gastric cancer.

Background/aims: The MiroCam MC2000 (MC2000) is a double-tip capsule with a camera on each side. It is designed to provide more extensive visualization of the small bowel mucosa, potentially reducing the chance of missing lesions. This study aimed to compare the detection rates for lesions in the ampulla of Vater (AoV) and the small bowel of the MC2000 and the PillCam SB3 (SB3) for patients with suspected small bowel bleeding.

Methods: This prospective, multicenter, randomized crossover trial compared the lesion detection capabilities of the MC2000 and SB3 capsules, ingested one hour apart by patients with suspected small bowel bleeding. The primary outcome was the detection of lesions in the AoV, while the secondary outcome was the assessment of the detection of P1 and P2 lesions, known underlying causes of small bowel bleeding.

Results: There was no significant difference in AoV lesion detection rates between the devices. However, MC2000 demonstrated significantly greater detection of red spots in patients with visible bleeding (p=0.018) and tended to detect a greater number of small bowel lesions, including P2 lesions. Minor complications included device stasis, with fewer incidents with the MC2000 than with the SB3, and one instance of small bowel retention due to ulcers.

Conclusions: The MC2000's dual-camera system appears to enhance the detection of small bowel lesions over the SB3, especially for more important lesions. These findings suggest that the MC2000 may offer superior diagnostic capabilities for patients with suspected small bowel bleeding, potentially leading to better clinical outcomes (this trial registered KCT0005591).