Gastroenterology Report最新文献

Background: Obesity is recognized as a prominent contributing factor for pancreatic diseases; however, the mechanisms remain elusive. We aimed to identify the mediating role of circulating proteins in these associations.

Methods: A two-step Mendelian randomization (MR) was conducted to investigate associations between nine obesity indicators, thousands of circulating proteins, with three pancreatic diseases (acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma). Colocalization analyses were performed to validate these associations. Protein mediating networks among obesity indicators and pancreatic diseases were investigated by mediation analysis.

Results: Genetically predicted circulating levels of 4, 2, and 2 proteins were associated with acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma, respectively. In mediation analysis, decreased chymotrypsin B2 (CTRB2) levels mediated 1.03% (95% CI [confidence interval] 0.02%-2.03%) of the effects of body mass index on acute pancreatitis. Increased R-spondin 3 (RSPO3) levels mediated the effects of body mass index (2.95%, 95% CI 0.18%-5.73%), body fat percentage (4.53%, 95% CI 1.11%-7.96%), waist-hip ratio (8.48%, 95% CI 3.11%-13.86%), and visceral adipose tissue (3.93%, 95% CI 0.64%-7.22%) on acute pancreatitis. We also found increased klotho beta (KLOTB) levels mediated the effects of waist-hip ratio (7.01%, 95% CI 3.30%-10.71%) and visceral adipose tissue (8.98%, 95% CI 4.55%-13.41%) on chronic pancreatitis, and decreased receptor tyrosine kinase-like orphan receptor 1 (ROR1) levels mediated the effects of body mass index (10.39%, 95% CI 3.36%-17.42%) and visceral adipose tissue (6.29%, 95% CI 1.00%-11.58%) on pancreatic carcinoma.

Conclusions: The MR suggests that circulating CTRB2, RSPO3, KLOTB, and ROR1 proteins may mediate associations between obesity and pancreatic diseases.

Background: The gender, age, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (GAAD) score is a recent predictive tool for hepatocellular carcinoma (HCC) but lacks comparison with the AFP, Sex, Age, and Protein induced by vitamin K absence-II (ASAP) score, which uses similar parameters with different assays and formulas. Our study aimed to evaluate the performance differences between these two scores.

Methods: Blood samples from 622 patients with chronic liver diseases at Songklanagarind Hospital between 20 April 2023 and 31 December 2023 were analyzed. The cutoffs for the ASAP and GAAD scores were established as 0.526 and 2.570, respectively, and HCC diagnoses followed the European Association for the Study of the Liver (EASL) or the American Association for the Study of Liver Diseases (AASLD) guidelines.

Results: HCC diagnoses were observed in 28.6% of patients, with 48.3% diagnosed with early-stage diseases (Barcelona Clinic Liver Cancer stage 0 = 23, A = 63). Hepatitis B virus infection (40.4%) and metabolic dysfunction-associated steatotic liver disease (21.3%) were predominant causes. The area under the receiver operating characteristic curve (AUROCs) of the ASAP and GAAD scores for predicting all-stage HCC were comparable (0.933 vs 0.937, P = 0.578). For early-stage HCC, AUROCs were 0.880 (ASAP) and 0.891 (GAAD) (P = 0.353). Sensitivity and specificity for predicting all-stage HCC were 83.15% and 91.44% (ASAP), and 82.58% and 89.64% (GAAD), respectively; these values for early-stage HCC were 66.28% and 91.44% (ASAP) and 67.44% and 89.64% (GAAD). Subgroup analyses by cirrhosis and etiology showed no significant differences. New cutoff values of -0.083 (ASAP) and 1.725 (GAAD) were identified for at least 80% sensitivity and specificity for predicting early-stage HCC.

Conclusion: Both the GAAD and ASAP scores demonstrated excellent and comparable abilities in HCC detection across all stages, unaffected by cirrhosis or etiological differences.

Background: This study aimed to explore the regulation of Ras-related C3 botulinum toxin substrate1 (Rac1) on the intestinal barrier function in colitis and explore its molecular mechanism of regulation on tight junctions.

Methods: A dextran sulfate sodium (DSS)-induced colitis mouse model was used. The diseases activity index (DAI) was calculated daily. Epithelial permeability was measured. Colon sections were stained with hematoxylin and eosin, and the histological severity was analysed. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyse the messenger ribonucleic acid (mRNA) level of Rac1, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), and occludin in the colon. Western blot was used to detect occludin protein expression.

Results: Colitis mice showed increased DAI and histological scores, reduced colon length, and impaired epithelial permeability, which were significantly alleviated by the administration of Rac1 inhibitor NSC23766. The level of inflammatory genes including interleukin 6 (IL-6), myeloperoxidase and NOX1 in the colon tissue were elevated in colitis mice, while the administration of NSC23766 remarkably reduced the expression of these genes. Western blot analysis showed that the occludin protein level was suppressed by DSS, while NSC23766 treatment restored the expression of occludin in DSS mice.

Conclusions: Rac1 inhibitor NSC23766 attenuates symptoms, colonic inflammation, and intestinal permeability in a DSS-induced colitis model. These effects may be attributed to the suppression of inflammatory responses and DSS-induced damage of intestinal integrity.

Gastrointestinal stromal tumors (GISTs) originate from mesenchymal cells and account for ∼1% of primary malignant tumors in the digestive system. They are diagnosed based on characteristic immunohistochemical staining pattern, including CD117 and DOG1, as well as genetic analysis for mutations in the KIT and platelet-derived growth factor receptor α genes. Extragastrointestinal stromal tumors (EGISTs) share very similar morphology with GISTs but arise outside the gastrointestinal tract. The most common locations for EGISTs are the omentum, mesentery, retroperitoneum, and pancreas, followed by the liver, vagina, and prostate. The mean age of presentation of these tumors is in the sixth decade of life and tumor dimensions at different locations typically range from 7 to 15.8 cm. Most of these tumors are unifocal and of the spindle cell type. GISTs generally have a better prognosis than EGISTs, with cumulative 5-year survival rates of 85% for GISTs and 38%-60.9% for EGISTs. Among EGISTs, omental tumors have higher overall survival than mesenteric or retroperitoneal tumors. Additionally, age of >60 years, male sex, larger tumor size, higher mitotic rate, and nuclear pleomorphism are associated with worse prognosis in EGISTs.

Background: Appendicitis imposes a substantial healthcare burden globally, yet comprehensive insights into its disease burden in Europe remain limited. This study assesses regional trends, disparities and high-burden countries for appendicitis in Europe.

Methods: Data on appendicitis-related incidence, mortality and disability-adjusted life years (DALYs) were extracted from the Global Burden of Disease 2019 study. Joinpoint regression analyzed temporal trends, while health inequality and quadrant analyses identified socio-demographic disparities and priority countries.

Results: In 2019, Europe's age-standardized incidence rate (ASIR) for appendicitis was 266.47 per 100,000, exceeding the global average (229.86 per 100,000). However, Europe's age-standardized mortality rate and age-standardized DALY rate were lower than the global averages. From 1990 to 2019, the average annual percentage change (AAPC) for the ASIR was 0.50%, whereas the AAPCs for the age-standardized mortality rate and age-standardized DALY rate were -3.02% and -2.20%, respectively. Finland was the sole exception, showing a reduced ASIR (AAPC: -0.20%). Health inequality analysis revealed that the burden of DALYs disproportionately affected less developed European nations. However, there was a notable improvement over the past three decades. The slope index of inequality decreased from -7.32 DALYs per 100,000 in 1990 to -1.02 DALYs per 100,000 in 2019, and the relative concentration index fell from -11.04 to -2.58 during the same period. Among the 43 countries, Bulgaria and Austria had the highest 2019 DALY burdens.

Conclusions: Appendicitis persists as a critical public health challenge in Europe, necessitating targeted resource allocation and policy interventions in high-burden countries to address persistent health inequalities.

Background: Tumor location affects rectal cancer management, but no consensus exists on criteria. The anterior peritoneal reflection (aPR), an anatomical landmark, shows potential for defining tumor location but requires clinical validation. This study evaluated the utility of aPR in guiding neoadjuvant chemoradiotherapy (nCRT) decisions and predicting lateral lymph node (LLN)/distant metastasis patterns.

Methods: This single-center retrospective cohort analyzed data from Peking Union Medical College Hospital (Beijing, China) between January 2016 and August 2022. Magnetic resonance imaging (MRI)-measured aPR parameters were pathologically validated. Patients were stratified by aPR-based definition and tumor height (10 cm). Kaplan-Meier survival curves, log-rank tests, and Cox regression were used for prognostic analysis.

Results: Among 588 patients (439 tumors ≥5 cm from the anal verge), MRI identified aPR with an accuracy of 95.4%. For tumors ≥5 cm, aPR-defined middle-to-low rectal cancer showed lower 3-year disease-free survival (DFS) rate than the upper rectal cancer (P = 0.010), while their 3-year overall survival (OS) rates were comparable. Conversely, 10-cm-defined classification showed no DFS or OS differences (both P > 0.2). Cox regression confirmed aPR-defined classification as an independent DFS predictor (HR = 3.19, P = 0.014), while 10-cm classification was non-predictive. nCRT with tumor regression grade (TRG) 0-1 trended toward improved DFS compared with direct surgery (HR = 0.56, P = 0.072). The independent protective effect of nCRT with TRG 0-1 for DFS was exclusive to the aPR-defined middle-to-low rectal cancer subgroup (HR = 0.45, P = 0.026) and not observed in the 10-cm subgroup. aPR-defined classification was independently associated with LLNs on MRI and postoperative pulmonary metastasis.

Conclusion: aPR may guide nCRT decision-making and predict LLN metastasis and postoperative distant organ metastasis.