Digestive Diseases and Sciences最新文献

Introduction: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases in the western world. Proton pump inhibitors (PPIs) are the cornerstone of GERD management however a subset of patients seeks for (natural) alternative therapies. Benesco™ is an over-the-counter supplement, of which the active ingredient is quercetin and has a presumed positive effect on esophageal barrier function. The aim of this study was therefore to evaluate the effect of benesco™ on esophageal sensitivity, mucosal barrier function, and reflux symptoms.

Methods: Patients with GERD were evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy, and esophageal biopsies.

Results: 8 patients (3 men, median age 45 (34-64)) were included. The perfusion sensitivity score (PSS) did not change significantly after treatment with benesco™ (90.5 (21.4-129.7) to 62.5 (16.4-96.9) p = 0.123). Esophageal sensitivity based on the maximum reported VAS score during the esophageal acid perfusion test did not change significantly after treatment with benesco™ (7.4 (5.3-9.8) to 7.7 (5.3-8.7) p = 0.482). Furthermore, no effects were seen on measures of mucosal barrier function such as extracellular in vivo impedance (ETIS) (6807 (5153-8883) Ω·m vs 6702 (5106-7847) Ω·m, p = 0.575), in vitro transepithelial electrical resistance (TEER) (183 (153-204) Ω.cm2 vs 201 (128-250) Ω.cm2, p = 1.000), or fluorescein flux (896 (73-1922) nmol/cm²/h vs 811 (187-2693) nmol/cm²/h, p = 0.237).

Conclusion: We did not observe an improvement of acid perception, mucosal barrier function, or reflux symptoms by benesco™ in this study.

Trial registration: Dutch Trial Register number: NL9324.

Background: Reports on postoperative bleeding after esophageal endoscopic resection are limited.

Aims: This study aimed to identify the clinical characteristics and risk factors for postoperative bleeding following endoscopic resection of esophageal neoplasms.

Methods: This single-center, retrospective study included consecutive patients who underwent endoscopic resection for esophageal squamous cell carcinoma or squamous intraepithelial neoplasm between January 2018 and December 2022. We investigated the incidence, timing, severity, and risk factors for postoperative bleeding.

Results: Of 1288 patients, 1062 (82%) underwent endoscopic submucosal dissection, and 226 (18%) underwent endoscopic mucosal resection. Postoperative bleeding occurred in seven (0.5%) patients (95% confidence interval [CI] 0.2-1.1%; median postoperative day 8 [range, 4-17 days]). In these seven patients, hemoglobin concentration decreased by a median of 3.0 g/dL (range, 1.6-6.8 g/dL). Antithrombotic agent use, resection wound circumference, and specimen size were significantly associated with postoperative bleeding (P < 0.001, P = 0.002, and P = 0.024, respectively). Among 43 patients who received direct oral anticoagulants (DOACs), postoperative bleeding occurred in four (9%) patients (95% CI 2.6-22.1%). DOACs were significantly associated with postoperative bleeding even after propensity score matching (4/40 [10%] vs. 0/80 [0%], respectively; P = 0.011).

Conclusions: The overall bleeding rate following esophageal endoscopic resection was 0.5%, with a delayed onset, leading to anemia. DOACs emerged as the most significant risk factor for postoperative bleeding.

Background: Colorectal cancer (CRC) is an aggressive malignancy among malignant tumours, with a high incidence globally. LINC01614, a long non-coding RNA, has been identified as an essential regulator in multiple cancer types. However, its biological functions and underlying molecular mechanisms in CRC remain largely unknown.

Methods: In this study, we employed RT-qPCR to assess the expression levels of LINC01614 in CRC samples. In vitro, glucose metabolism experiments were conducted to evaluate glucose metabolism in cells. The binding relationship between miR-4443, PFKFB3, and LINC01614 was confirmed through fluorescence reporter gene detection. The subcellular localization of LINC01614 in CRC cells was determined using FISH and subcellular fractionation experiments. Additionally, a mouse subcutaneous tumor model was established for in vivo experiments.

Results: Our findings reveal that LINC01614 is upregulated in CRC tissues. Silencing of LINC01614 suppresses the malignant behaviors of CRC cells, including cell proliferation, invasion, migration, and aerobic glycolysis. Furthermore, we discovered that LINC01614 promotes the expression of PFKFB3. Additional experiments demonstrated that LINC01614 binds to miR-4443, leading to the upregulation of PFKFB3 expression. Further experiments confirmed that the LINC01614/miR-4443/PFKFB3 axis promotes CRC cell malignancy by enhancing aerobic glycolysis. Additionally, we found that STAT1 promotes the transcription of LINC01614.

Conclusion: These findings uncover a novel regulatory pathway wherein STAT1-induced LINC01614 enhances PFKFB3 expression by sponging miR-4443, thereby accelerating CRC development. This understanding may lead to novel therapeutic strategies for CRC treatment.

Background: Colorectal cancer (CRC) diagnoses are frequently made through emergency presentations (EPs), a new cancer diagnosis following an emergency care episode or unplanned inpatient admission. The extent and implications of EPs are not well known in the Veterans Affairs (VA) health system, where robust CRC screening protocols exist. The impact of the COVID-19 pandemic on the route of CRC diagnosis also remains unclear.

Methods: We conducted a retrospective cohort study of all incident CRC cases diagnosed nationally in the VA health care system from 2017 to 2021. We applied a previously validated algorithm to identify CRC EPs and used multivariable logistic regression and Cox proportional hazards models to examine the associations between EPs and CRC stage, treatment, and mortality.

Results: We identified 9,096 patients with CRC, 28.1% of whom had EPs, with the proportion of EPs increasing over the study period from 26.4% in 2017-2019 to 31.4% in 2020-2021. Patients with EPs were more likely to have advanced stage disease (adjusted OR 1.70; 95% CI 1.53-1.88) and less likely to receive cancer treatment (adjusted OR 0.65; 95% CI 0.56-0.75) than patients without EPs. Patients with EPs also had significantly higher mortality risk (adjusted HR 1.70; 95% CI 1.56-1.84).

Conclusion: In a large cohort of patients diagnosed with CRC, we found EPs to be common and independently associated with worse cancer outcomes. EPs also increased during the COVID-19 pandemic. Interventions are needed to reduce potentially avoidable EPs and improve outcomes of patients with CRC diagnosis.

Background/aims: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

Methods: We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or CRC through 12/2023 for patients without polyps on index colonoscopy (negative colonoscopy) to patients with polyps (positive colonoscopy). We examined risk factors for incident adenomas using Cox regression models.

Results: Of 2096 patients, 1293 (61.7%) had negative index colonoscopy and 803 (38.3%) had positive index colonoscopy. Overall, 411 patients (19.6%) underwent subsequent colonoscopy with incident adenomas in 241 patients and no incident CRC over mean 12.5 years. The incidence rate of advanced adenomas was 2.08 per 100 person-years after positive index colonoscopy compared to 0.65 per 100 person-years after negative index colonoscopy (age-adjusted incidence rate ratio 3.08, 95% CI 1.27-7.48). Non-Hispanic white race was the strongest risk factor for incident adenomas among patients with negative index colonoscopy.

Conclusions: We found a low likelihood of advanced adenomas and no interval CRC following negative index colonoscopy after positive FOBT/FIT. Non-Hispanic white race was a risk factor for incident adenomas, and these patients may warrant closer surveillance.