Saudi Journal of Gastroenterology最新文献

Background: Cuproptosis is a novel pathway that differs from other forms of cell death and has been confirmed to be applicable for predicting tumor prognosis and clinical treatment response. However, the mechanism underlying the resistance of colorectal cancer (CRC) to cuproptosis at the molecular level has not been elucidated.

Methods: Using bioinformatics analysis, the expression of CCAAT/enhancer-binding protein beta (CEBPB) in CRC tissues and its enrichment in biological processes were detected. Quantitative reverse transcription polymerase chain reaction and western blotting (WB) were employed to test the expression of CEBPB in CRC cells. WB was utilized to assess the levels of proteins related to cuproptosis and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. The MTT assay was used to test cell viability. Cell proliferation was assessed by a colony formation assay. Transwell assays were used to measure cell migration and invasion ability. DLAT-aggregate formation was determined by immunofluorescence.

Results: CEBPB was highly upregulated in CRC cells to enhance cell viability, proliferation, migration, and invasion. CEBPB was strongly implicated in copper ion homeostasis and the mTOR signaling pathway in CRC. In a CRC cuproptosis cell model, rescue experiments revealed that a PI3K/AKT/mTOR pathway inhibitor attenuated the promoting effect of CEBPB overexpression on the PI3K/AKT/mTOR pathway and rescued the sensitivity of CRC to cuproptosis.

Conclusion: This work demonstrated that CEBPB can activate the PI3K/AKT/mTOR signaling pathway, thereby decreasing the sensitivity of CRC to cuproptosis. These data suggested that targeting CEBPB or the PI3K/AKT/mTOR pathway may enhance the sensitivity of CRC patients to cuproptosis, providing a combined therapeutic strategy for cuproptosis-induced therapy.

Abstract: Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in outpatient general medicine and gastroenterology clinics. GERD may present with classic esophageal symptoms, extraesophageal symptoms, or mixed symptoms. The diagnosis and treatment of GERD are challenging due to the variety of symptoms and multifactorial pathophysiology. Since there is no consensus on the diagnosis and treatment of GERD in Saudi Arabia, the Saudi Gastroenterology Association established an expert group to formulate a consensus on the clinical care pathway for the diagnosis and treatment of GERD to update health-care providers in Saudi Arabia. The expert group reviewed the literature including recently published international guidelines, clinical trials, and expert opinion and conducted virtual and in-person meetings. A total of 22 statements on the definition, diagnosis, and treatment of GERD were formulated, and three algorithms for the clinical care of GERD were developed with a detailed description for each step. The expert group endorsed the new definition of GERD, the practical principles of interpretation of the diagnostic GERD evaluation, and the practical guidance for GERD treatment including medical, surgical, and endoscopic therapy. The expert group recommends further studies to investigate local data on the diagnosis and treatment of GERD.

Background: The medical treatment of ulcerative colitis (UC) includes the use of biological agents such as vedolizumab, a gut-selective alpha4beta7 (ɑ4β7) antagonist. The mechanism of action of vedolizumab involves interfering with leukocyte trafficking into the gut vasculature, which halts inflammation. Due to this mechanism of action, concerns have arisen regarding an increased risk of gut infections, specifically, clostridium difficile infection (CDI). The aim is to provide clarity regarding the association between the use of vedolizumab as a therapy for ulcerative colitis and the risk of developing CDI.

Methods: A systematic literature review was conducted, starting with the scoping search, followed by backward snowballing parallel with keyword-based search to identify related articles. A quality assessment was conducted on the initially selected articles and excluded low-quality papers.

Results: Pooled analyses indicated that there was no significant association between the use of vedolizumab and the risk of developing CDI (effect size = 0.03 [-0.02, 0.07]).

Conclusions: Vedolizumab does not increase the risk of CDI in patients with UC. Further studies are needed to confirm these findings.

Background: In Saudi Arabia (SA) no data are available on precancerous stomach lesions (PSLs) or the associated risk factors. We aimed to identify PSLs and investigate factors associated with PSLs and their progression.

Methods: This 7-year prospective study screened for PSLs in asymptomatic Saudi patients aged 45-75 years in central SA ( n = 35,640). Those who had high-sensitivity guaiac fecal occult blood tests (HSgFOBT+) and negative colonoscopy results ( n = 1242) were subjected to upper GI endoscopy to identify PSLs and were followed up every 3 years or earlier, depending on the type of PSL. Factors associated with PSLs were investigated.

Results: The 7-year participation rate was 86.9% (1080/1242). The 7-year prevalence of PSLs was 30.9% (334/1080). The incidence rate of PSLs was 134 new cases/100,000 population/year, total population at risk - 35,640 and 44.3 new cases/1,000 persons/year among the 1080 participants with HSgFOBT+ and negative colonoscopy results. Among the 334 participants with PSLs, 8 (2.4%) had neoplastic progression to GC during the surveillance period. Age, Helicobacter pylori infection, smoking status, a diet with preserved salty foods, low income, and a family history of GC were associated with PSLs.

Conclusions: The incidence of GC is low in central SA, but screening for PSLs among participants with HSgFOBT+ and negative colonoscopy findings may contribute to the early detection and subsequent treatment of GC. HP eradication, not smoking, normal body weight, and adhering to a healthy diet seem to be potential factors associated with the development of PSLs. Further studies are needed to search if such interventions would decrease the incidence of PSLs and progression to early GC.

Background: This study observed the clinical outcome of radiotherapy to extensive intrahepatic targets for advanced hepatocellular carcinoma (HCC) in a single institution.

Methods: From September 2009 to July 2021, patients who underwent fractionated radiotherapy to a planning target volume (PTV) of over 100 ml with biological effective dose >30 Gy 10 for advanced HCC were enrolled. Overall survival (OS) and radiation-induced liver toxicity (RILD) were evaluated. RILD was defined as an increase in Child-Pugh (CP) score ≥2 or liver function tests ≥2.5 times at 3 months after the end of radiotherapy.

Results: A total of 136 patients were evaluated. Eighty-nine patients had portal vein tumor thrombus (PVTT), 37 patients were in CP B stage, and the median radiation dose to PTV was 48.8 Gy 10 . The median OS was 12.3 months. The factors most affecting OS were PVTT ( P = 0.001), PTV (>500 ml, P = 0.001), incomplete coverage of the intrahepatic tumor ( P = 0.004), and CP B ( P = 0.006) in Cox regression. RILD occurred in 22.4% of the patients and was affected by PVTT ( P = 0.003), PTV ( P = 0.010), pretreatment bilirubin levels (>1.5 mg/ml, P = 0.016), and the mean normal liver dose (MNLD) (≥ EQD 2 18 Gy 3 , P = 0.021) in binary logistic regression. As the PTV was in excess of >500 ml, RILD developed in 30.2% of patients and the prognostic importance of pretreatment bilirubin levels ( P = 0.006) and the MNLD ( P = 0.014) increased.

Conclusions: As PTV is more extensive, the bilirubin level and the MNLD have to be taken into consideration for safe radiotherapy, in addition to the traditional prognostic factors.

Background: Self-care is one of the basic principles in the management of chronic diseases, which influences follow-up and adherence to treatment. Therefore, the current study was conducted with the aim of comparing the effect of teach-back (TB) and a smartphone application on adherence to treatment in patients with inflammatory bowel disease (IBD).

Methods: The current clinical trial was conducted among 80 patients with IBD in Mashhad, Iran, in 2021-2022. Self-care education (diet, personal and social relationships, medications, sleep, physical activity, sexual relationships, etc.) was provided through TB method in one group and by using a smartphone application in another group. The control group only received the routine education. A checklist for demographic information and the adherence questionnaire in patients with chronic diseases were used for data collection.

Results: Patients' mean age was 38.73 ± 10.32 years. The majority of patients had ulcerative colitis (81%) and were married (67%). Mean and standard deviation score of adherence to treatment were the same in all three groups before the intervention ( P = 0.668). The mean post-test scores of adherence to treatment in the TB, application, and control groups were 170.04 ± 14.19, 167.99 ± 11.59, and 159.60 ± 10.94, respectively. The difference was statistically significant ( P = 0.003). A significant difference was observed in regards to the mean post-test scores of adherence to treatment between TB and control groups ( P = 0.004) and app and control groups ( P = 0.048). However, the difference between TB and app groups was not significant ( P = 0.989).

Conclusions: TB method and smartphone application have the same effect on adherence to treatment in patients with IBD. Due to the usability and cost-effectiveness of smartphone applications, this method can be used by health-care providers to educate this group of patients.

Background: Several investigations suggested correlation between microscopic colitis (MC) and celiac disease (CD). This study aimed to examine this relationship using large-sized, population-based data with adequate control for confounding factors.

Methods: This study employed the National Inpatient Sample (NIS) database over 4 years (2016-2019). Patients with/without MC in the presence/absence of CD were identified through ICD-10 codes. Univariate and multi-variate analyses involving odds ratios (OR) and 95% confidence intervals (CI) were performed.

Results: Overall, 26,836,118 patients were analyzed. Of whom, 6,836 patients had MC (n = 179 with CD and n = 6,657 without CD). The mean hospital stay was not significantly different between both groups (5.42 ± 5.44 days vs. 4.95 ± 4.66 days, P = 0.202). The univariate analysis revealed a significant association between MC and CD (OR = 22.69, 95% [19.55, 26.33], P < 0.0001). In the multi-variate analysis, which adjusted for potential confounders including age, race, hospital region, hospital teaching status, ZIP income, smoking status, alcohol overuse, hypertension, diabetes mellitus, lipidemia-related disorders, non-steroidal anti-inflammatory drug use, and selected auto-immune diseases, the association remained significant (OR = 15.71, 95% CI [13.52, 18.25], P < 0.0001). Moreover, in patients with MC, the presence of CD emerged as a significant, independent variable of in-hospital mortality in univariate (OR = 2.87, 95% [1.14, 7.21], P = 0.025) and multi-variate (OR = 3.37, 95% CI [1.32, 8.60], P = 0.011) analyses.

Conclusion: This study establishes a probable link between MC and CD, backed by both univariate and multi-variate analyses, while also identifying CD as an independent risk factor for increased mortality among MC patients. These findings need to be validated in real-world clinical studies.

Background: Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data.

Methods: A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution.

Results: The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness.

Conclusion: In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.