Gastroenterology Report最新文献

Background and aims: This study explored the efficacy of a prophylactic intestinal decompression tube in reducing the incidence of post-endoscopic submucosal dissection electrocoagulation syndrome (PECS).

Methods: A total of 157 eligible patients with colorectal mucosal lesions scheduled for endoscopic submucosal dissection (ESD) were prospectively recruited; after drop out 11 patients, 146 patients were randomly assigned to an experimental group (group 1, n = 73) or control group (group 2, n = 73). Patients in the experimental group underwent placement of an intestinal decompression drainage tube after ESD, while the control group received no additional treatment after ESD. The primary outcome was the incidence of PECS. Secondary outcomes included the incidence of postoperative complications, time to removal of the intestinal decompression tube, the degree of abdominal pain as measured by the visual analog scale (VAS), and the participants' self-rated comfort level with the intestinal decompression tube.

Results: A total of 146 patients (n = 73 per group) were finally analyzed between July 2022 and February 2023. All tumors were successfully resected en bloc. A significant difference in the incidence of PECS was found between group 1 and group 2 (5.5% vs 16.4%; P = 0.034). Precisely, 61.6% of patients felt painless for intestinal decompression tube, and no severe or unbearable pain was reported.

Conclusions: The placement of intestinal decompression drainage tube could reduce the incidence of PECS after colorectal ESD, which might play a preventive role in the occurrence of PECS.

Background: Colorectal cancer (CRC) is the third-most-common malignancy and the second-leading cause of cancer-related deaths worldwide and current screening methods such as guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and colonoscopy have their own pros and cons. This study aimed to assess the effectiveness of a fecal DNA methylation test by using methylated SDC2 (mSDC2) as the epigenetic biomarker for detecting CRC in a screening-naïve population.

Methods: Fecal mSDC2 test and FIT were simultaneously performed on eligible 40- to 74-year-old adults of a regional township in China. Subjects with positive results were recommended for colonoscopy. Data of positivity rates, positive predicted values (PPVs), and detection rates associated with clinical characteristics were analysed.

Results: The positivity rate of mSDC2 was 7.6% for 10,578 participants with valid results from both fecal mSDC2 test and FIT. With an adherence rate of 63.8% to colonoscopy referral, 25 CRCs, 189 advanced adenomas (AAs), and 165 non-advanced adenomas (NAAs) and polyps were detected. The PPVs of mSDC2 were 4.93%, 37.28%, and 32.54% for CRC, AA, and non-advanced lesions, respectively. When the CRCs and AAs were counted as positive findings, the fecal mSDC2 test showed a higher detective rate than FIT (relative risk [RR], 1.313 [1.129-1.528], P < 0.001). When NAAs and polyps were also specified as treatable lesions, the mSDC2 test was more effective in detecting these benign growths (RR, 1.872 [1.419-2.410]; P < 0.001). A combination of mSDC2 and FIT detected 29 CRCs, 298 AAs, and 234 NAAs and polyps. Overall, the fecal mSDC2 test had a higher detection rate for both advanced and non-advanced colonic lesions. The false-positive rate of the fecal mSDC2 test was comparable to that of FIT (RR, 1.169 [0.974-1.403]; P = 0.113).

Conclusions: The single-target stool-based mSDC2 test can effectively and accurately detect CRC and precancerous lesions in a large-scale CRC-screening program.

Trial registration number: NCT05374369.

Background: Pancreatic cancer (PC) is a heterogeneous disease with various histological and molecular subtypes. This study aimed to provide updated epidemiological estimates, survival outcomes, and treatment information for PC based on histological subtypes in the USA.

Methods: Data from the US Cancer Statistics and Surveillance, Epidemiology, and End Results (SEER)-17 databases (2000-2020) were used, including adults aged ≥20 years who were diagnosed with PC. The trends of incidence and prevalence by histological types were calculated by using the Joinpoint Regression model. Survival by histological type was analysed by using Kaplan-Meier curves and log-rank tests for group comparisons.

Results: Overall, the age-adjusted PC incidence per 100,000 increased from 9.54 to 12.05 in SEER-17 and from 9.75 to 12.19 in the US Cancer Statistics between 2001 and 2019. A further SEER-17 study comprised 113,681 PC cases that were sorted by histologic type between 2000 and 2020. The incidence per 100,000 of invasive intraductal papillary mucinous neoplasm (IPMN) and invasive mucinous cystic neoplasm (MCN) decreased (IPMN from 0.67 to 0.20 and MCN from 0.05 to 0.01) whereas that of other histological subtypes increased. Survival analysis indicated the best outcomes for solid pseudopapillary tumors and the poorest for squamous cell carcinoma. At the localized stage, the proportion of surgery in the treatment modalities varied depending on the biological behavior; the proportion of surgery for pancreatic neuroendocrine tumor was the highest and that for pancreatic ductal adenocarcinoma (PDAC) was the lowest. At the distant metastasis stage, a chemotherapy-based regimen remained the primary treatment of PDAC, pancreatic neuroendocrine tumor, and IPMN.

Conclusions: PC incidence and prevalence have been increasing. The incidence of IPMN and MCN decreased whereas that of other subtypes increased. Treatment distribution varies among subtypes and stages.

IgG4-related cholangitis (IRC) is a chronic cholestatic liver disease that often occurs concomitantly with autoimmune pancreatitis type 1. Both conditions are manifestations of IgG4-related disease, a systemic autoimmune-mediated fibroinflammatory disorder. Patients often present with jaundice and weight loss, mimicking hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer. Accurate diagnosis is challenging due to the absence of pathognomonic findings but can be achieved using the HISORt criteria (histology, imaging, serology, other organ involvement, and response to immunosuppressive therapy). Early diagnosis is critical to avoid unnecessary surgery and prevent progression to liver fibrosis or cirrhosis. IRC responds well to corticosteroid therapy, though relapses are common, necessitating long-term immunosuppressive treatment in many cases. Steroid-sparing agents for remission induction and maintenance therapy comprise immunomodulators, such as azathioprine, as well as B-cell depletion therapies, such as rituximab. This review provides a structured clinical overview of the diagnosis, differential diagnosis, and therapy, including novel therapeutic options, such as inebilizumab, for this rare yet severe condition. A key focus is on long-term surveillance strategies, which include laboratory tests, imaging (contrast-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography, ultrasound, endosonography), and, particularly in patients with fibrotic bile duct strictures, endoscopy (endoscopic retrograde cholangiopancreatography, cholangioscopy).

Background: Delayed upper gastrointestinal transit during small bowel capsule endoscopy (SBCE) can lead to incomplete or failed examinations but can be treated by endoscopic-assisted intervention (EAI). The aim of this study was to investigate the latest possible timing of EAI.

Methods: Patients who underwent SBCE and received EAI between July 2007 and December 2020 were retrospectively reviewed. A novel T-value was developed that accounted for the varied battery life of different generations of PillCam when determining the latest possible timing of EAI, where T is calculated as EAI time/[minimum battery life of the PillCam minus small bowel transit time (6 h)] × 100%. Patients were divided into two groups based on the cut-off value of the receiver operating characteristic curve: early EAI (group A, T < 76.3%) and late EAI (group B, T ≥ 76.3%). The primary outcome was the completion rate (CR), and the secondary outcome was the detection rate. The latest possible timing of EAI (h) was calculated according to the T-value formula and further verified in our recent data set.

Results: This study included 108 patients. The CR was significantly higher in group A than in group B (79.2% vs 58.2%; P = 0.018). Late EAI was an independent predictor of incomplete SBCE (odds ratio = 2.900; 95% confidence interval, 1.193-7.053). The latest possible timing of EAI was 1.5 h and 4.6 h from the start of the examination for PillCam SB1 and PillCam SB2/3, respectively.

Conclusions: Early EAI was associated with higher CR. The latest possible timing of EAI was 1.5 h for PillCam SB1 and 4.6 h for PillCam SB2/3 from the start of the examination.

Background: Intestinal ischemia/reperfusion (II/R) is a severe condition with high mortality and limited treatment options. Extracellular vesicles that are derived from bone marrow mesenchymal stem cells (BM-MSC-EVs) exhibit therapeutic potential in alleviating II/R injury. However, the mechanism by which BM-MSC-EVs fulfill this function requires further characterization. The ubiquitin-proteasome system plays an essential role in II/R, but the functions of individual ubiquitination regulators such as ubiquitin-specific proteases (USPs) in this process remain incompletely understood.

Methods: An II/R cellular model was established by using IEC-6 intestinal epithelial cells with oxygen-glucose deprivation/reperfusion (OGD/R) treatment. The expression of USPs was evaluated by using quantitative polymerase chain reaction and Western blot. The role of USP38 on the viability, apoptosis, migration, and reactive oxygen species (ROS) levels in OGD/R-treated IEC-6 cells were measured by using CCK-8, Annexin V/PI staining, transwell assay, and 2',7'-dichlorofluorescin diacetate (DCFDA) staining, respectively. The interaction between USP38 and BIRC5 was explored by using co-immunoprecipitation (Co-IP) and the ubiquitination level and stability of BIRC5 were examined by using Western blot. USP38-overexpressing BM-MSC-EVs were produced to treat OGD/R-treated IEC-6 cells.

Results: USP38 expression was significantly downregulated in OGD/R-treated IEC-6 cells. Incubation of these cells with BM-MSC-EVs substantially elevated the USP38 expression, resulting in improved viability, reduced apoptosis, enhanced migration, and decreased ROS levels. Furthermore, overexpression of USP38 in BM-MSC-EVs further enhanced their protective effect on OGD/R-treated IEC-6 cells. At the molecular level, USP38 interacts with and stabilizes BIRC5 by decreasing its ubiquitination. Knock-down of BIRC5 abolished the protective effect of excessive USP38 on OGD/R-treated IEC-6 cells.

Conclusion: USP38 protects intestinal epithelial cells from I/R injury by enhancing the stability of BIRC5.

Background: Gasdermin E (GSDME) is a newly identified pyroptosis executioner and is upregulated in the intestinal epithelial cell (IEC) of ulcerative colitis (UC) patients. However, the effects of epithelial GSDME on UC remain unknown.

Methods: Bone marrow chimera experiments were performed to investigate the role of GSDME in nonhematopoietic cells, mainly including IECs. An FITC-dextran assay was used to assess the integrity of the intestinal epithelial barrier.

Results: Gsdme^-/- chimeras that were reconstituted with wild-type bone marrow cells exhibited lower weight loss, disease activity index, colon shortening, and histology scores than wild-type chimeras after treatment with dextran sulfate sodium (DSS). However, Gsdme ^+/+ chimeras that were reconstituted with Gsdme-deficient bone marrow cells were not protected from DSS-induced colitis compared with wild-type chimeras. Importantly, DSS treatment activated Caspase-3 and cleaved GSDME to generate GSDME-N terminal fragments that are responsible for the induction of pyroptosis in IECs, but not in the intestinal lamina propria cell. Additionally, GSDME deficiency inhibited DSS-induced disruption of the intestinal epithelial barrier. Mechanistically, GSDME-mediated IEC pyroptosis is dependent on Caspase-3 activation, which is supported by the observation that the Caspase-3 inhibitor Z-DEVD-FMK inhibited DSS-induced GSDME cleavage in IECs.

Conclusions: We show that GSDME-mediated epithelial pyroptosis contributes to the development of DSS-induced colitis by promoting intestinal inflammation and disrupting the intestinal epithelial barrier.

Hepatocellular carcinoma (HCC) corresponds to the vast majority of liver cancer cases, with one of the highest mortality rates. Major advances have been made in this field both in the characterization of the molecular pathogenesis and in the development of systemic therapies. Despite these achievements, biomarkers and more efficient treatments are still needed to improve its management. Heparan sulfate (HS) chains are polysaccharides that are present at the cell surface or in the extracellular matrix that are able to bind various types of molecules, such as soluble factors, affecting their availability and thus their effects, or to contribute to interactions that position cells in their environments. Enzymes can modify HS chains after their synthesis, thus changing their properties. Numerous studies have shown HS-related proteins to be key actors that are associated with cellular effects, such as tumor growth, invasion, and metastasis, including in the context of liver carcinogenesis. The aim of this review is to provide a comprehensive overview of the biology of HS chains and their potential importance in HCC, from biological considerations to clinical development, and the identification of biomarkers, as well as therapeutic perspectives.