Gastroenterology Report最新文献

Introduction: Stool DNA testing based on methylated syndecan-2 (mSDC2) is a potential novel non-invasive screening test for colorectal cancer (CRC). This study aimed to assess its positive predictive value (PPV) in real-world practice.

Methods: This study retrospectively recruited consecutive patients with positive stool DNA-based SDC2 methylation tests from 18 hospitals between November 2016 and July 2021. Included patients were classified into the average-risk equivalent or increased-risk population and the previous-negative-colonoscopy or no-previous-colonoscopy groups. Multivariate logistic regression was conducted to investigate the risk factors that affect the detection of advanced colorectal neoplasia (ACN) in patients with a positive mSDC2 test. The primary outcome was the PPV for ACN.

Results: The overall PPVs for ACN, CRC, and colorectal neoplasia were 28.5%, 12.8%, and 44.6%, respectively. The PPV for ACN was higher in the no-previous-colonoscopy group than in the previous-negative-colonoscopy group (30.1% vs 18.5%, P = 0.008) and higher in the increased-risk population than in the average-risk equivalent population (41.1% vs 21.6%, P < 0.001). However, the PPV (18.5%) was still high for patients with a previous negative colonoscopy. For ACN detection in patients with a positive mSDC2 test, old age, increased risk, and smoking history were identified as independent risk factors; previous negative colonoscopy was identified as a protective factor.

Conclusions: The mSDC2 test, which has a high PPV for both ACN and CRC, is expected to be an alternative CRC screening strategy. Patients with a positive mSDC2 test might require a colonoscopy as soon as possible, even if the previous colonoscopy was negative.

Background: According to the Global Cancer Observatory 2020 report, pancreatic cancer occupies the 11th position among the leading causes of cancer-related mortality in both sexes, with nearly 500,000 deaths annually worldwide. This study aimed to evaluate the trend of mortality due to pancreatic cancer in Montenegro from 1990 to 2018 and to contribute to the effective planning of preventive strategies for pancreatic cancer as well as future health policies and initiatives.

Methods: We utilized national data on the causes of death from pancreatic cancer and codes 157 from the 9th and C25 from the 10th revision of the International Classification of Diseases. The trend was described by using Joinpoint, Poisson, and linear regression.

Results: Mortality rates of pancreatic cancer in Montenegro consistently increased (P < 0.05) for the overall level for both men and women, with the average annual percentage change (AAPC) in the AAPC order (95% confidence interval): 1.7% (0.9%-2.5%) overall, 1.3% (0.4%-2.1%) in men, and 2.2% (0.9%-3.5%) in women. The majority of those who died from pancreatic cancer were aged 65-74 years (32.7%), 55-64 years (26.3%), and 75-84 years (24.1%).

Conclusions: The persistent increase in pancreatic cancer mortality rates in Montenegro, observed in both men and women, highlights a concerning public health trend. With the highest proportion of deaths occurring among individuals aged 55-84 years, these findings underscore the urgent need for policymakers to implement a national strategy targeting early detection, prevention, and improved management, especially among the most affected age groups.

Background: We aimed to investigate long-term survival outcome in patients with locally advanced esophagogastric junction adenocarcinoma and upper third gastric adenocarcinoma (EGJ-UG adenocarcinoma) who underwent proximal gastrectomy (PG) or total gastrectomy (TG).

Methods: We searched and analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with T2-3 EGJ-UG adenocarcinoma receiving TG or PG were included. We performed a propensity score 1:2 matching, and matched datasets were generated and compared.We obtained the patients' long-term survival benefits according to stratification of surgical approaches.

Results: Of 1,291 patients identified from the SEER database, 901 (69.8%) patients received PG and 390 (30.2%) patients received TG. After matching, 584 patients in the PG group were matched by propensity score to 344 patients in the TG group. There were no differences in overall survival and cancer-specific survival in matched data between different surgical approaches. For patients with tumor size ≤4 cm, similar long-term survival was observed in patients receiving PG and TG. For patients with tumor size >4 cm, TG was associated with improved overall survival and cancer-specific survival compared with PG.

Conclusion: This study has shown similar survival outcomes between PG and TG for patients with T2-3 EGJ-UG adenocarcinoma and with tumor size <4 cm.

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.