TC-325 Superiority in Malignant Gastrointestinal Bleeding: An Individual Patient Data Meta-Analysis of Randomized Trials.

INTRODUCTION: The efficacy of topical hemostatic agents, recommended for peptic ulcer bleeding, remains poorly characterized in malignant gastrointestinal bleeding (GIB). METHODS: We performed an individual patient data meta-analysis assessing the efficacy of topical hemostatic agents in malignant GIB. The literature was searched using OVID MEDLINE, EMBASE, and ISI Web of Science databases (database inception to November 2023). Only randomized controlled trials (RCTs) comparing topical hemostatic agents with conventional endoscopic modalities in malignant GIB were included. Original RCT patient-level data were obtained. Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. Quality of the evidence was evaluated using the revised Cochrane risk-of-bias tool and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation approach. The primary outcome was immediate hemostasis; secondary outcomes were 30-day rebleeding and the composite measure of further bleeding (persistent bleeding or 30-day rebleeding). Other outcomes were all-cause mortality, adverse events, and need for additional nonendoscopic treatment. Odds ratios (ORs) from endpoint comparisons were pooled using logistic regression models. RESULTS: Overall, 985 citations were identified; 3 RCTs (n = 160 patients) were included with all assessing TC-325 (Hemospray). TC-325 achieved immediate hemostasis more often than conventional endoscopic modalities (OR 46.6, 95% confidence interval [CI] 5.89-369.1) (low-level certainty). Thirty-day rebleeding (OR 0.28, 95% CI 0.11-0.70) and further bleeding (OR 0.11, 95% CI 0.05-0.26) were both significantly lower with TC-325 (very-low-level certainty). All-cause mortality and need for additional nonendoscopic treatment did not differ between groups. No adverse events were reported. Subgroup analysis confirmed TC-325 superiority in patients with upper GIB. DISCUSSION: TC-325 seems superior to conventional endoscopic therapy in managing patients with malignant GIB. TC-325 results in improvements in immediate hemostasis, 30-day rebleeding, and further bleeding, based on very low-to-low certainties of evidence.

Saudi consensus guidance for the diagnosis and management of inflammatory bowel disease in children and adolescents.

ABSTRACT: The management of inflammatory bowel disease (IBD) in children and adolescents is challenging. Clear evidence-based guidelines are required for this population. This article provides recommendations for managing IBD in Saudi children and adolescents aged 6-19 years, developed by the Saudi Ministry of Health in collaboration with the Saudi Society of Clinical Pharmacy and the Saudi Gastroenterology Association. All 57 guideline statements are based on the most up-to-date information for the diagnosis and management of pediatric IBD.

The use of cap-mounted clips as a primary hemostatic modality in nonvariceal upper gastrointestinal bleeding: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Cap-mounted-clips, especially Over-The-Scope-Clip (OTSC™), are recommended for recurrent nonvariceal upper gastrointestinal bleeding (NVUGIB). There has been recent interest in their use as an initial hemostatic modality. We performed a systematic review of randomized controlled trials (RCTs) assessing cap-mounted clips' efficacy as a primary hemostatic modality in NVUGIB. METHODS: A literature search of MEDLINE, EMBASE, and ISI Web of Science databases up to April 2024 identified RCTs comparing cap-mounted clips to standard endoscopic therapy (SET) as a primary hemostatic modality in NVUGIB. The primary endpoint was the composite outcome of further bleeding (persistent or recurrent) at 30 days. Secondary outcomes included persistent bleeding at index endoscopy and 30-day rebleeding, individually. Other pertinent outcomes were also recorded. A meta-analysis was performed to determine pooled risk ratios (RRs), comparing cap-mounted clip to SET. Out of 516 citations, five RCTs (n = 555), all assessing OTSC™, were included. RESULTS: The composite outcome of further bleeding was lower with cap-mounted clip versus SET (RR = 0.33 [95% confidence interval {CI}: 0.20-0.54]). There was no difference in persistent bleeding at initial endoscopy (RR = 0.30 [95% CI: 0.07-1.30]), but 30-day rebleeding was lower with cap-mounted clip (RR = 0.38 [95% CI: 0.21-0.70]). There were no differences in other outcomes. Grading of the evidence ranged from very low to moderate, mainly due to risk of bias and imprecision. CONCLUSIONS: Cap-mounted clips may be an efficacious primary hemostatic modality, associated with a lower further bleeding at 30 days compared to SET in NVUGIB. However, due to limitations in existing evidence, further research must better characterize an optimal subgroup of patients benefiting most from this approach before adopting its routine use.

Peptic ulcer disease.

Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.

Eosinophilic esophagitis: Current concepts in diagnosis and management.

ABSTRACT: Eosinophilic esophagitis is an antigen-mediated chronic inflammatory disorder that has risen in incidence and prevalence over the past 2 decades. The clinical presentation is variable and consists of mainly esophageal symptoms such as dysphagia, heartburn, food impaction, and vomiting. Current management relies on dietary elimination, proton-pump inhibitors, and topical corticosteroids with different response rates and relapses after treatment discontinuation. With a better understanding of the underlying pathophysiology, many molecules emerged recently as targeted treatment including dupilumab (IL4/IL13 blocker), as the first FDA-approved biological treatment, which has changed the management paradigm.

The Saudi Gastroenterology Association consensus on the clinical care pathway for the diagnosis and treatment of GERD.

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.

Primary and Specialty Care Trainees' Perceptions About Proton Pump Inhibitor Use.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely prescribed with proven efficacy in many indications, yet longstanding controversy about potential adverse events persists. We aimed to acquire knowledge about perceptions of outpatient PPI long-term prescribing (≥8 wk) among primary and specialty care trainees at 2 Canadian Universities. METHODS: Family medicine, internal medicine, and gastroenterology trainees completed a web-based survey that included 20 clinical scenarios assessing trainee knowledge about PPI efficacy. Contextual PPI prescribing decisions were also elicited, balancing possible PPI indications versus side effects. Management strategies were compared between junior and senior trainees, as well as across training programs. RESULTS: Over a 4-month period,163 trainees (age <26 y: 12%; age 26 to 45: 88%; 59% females) participated in the survey (family medicine: 51%, internal medicine: 44%, and gastroenterology: 5%); 83% were considered junior residents. Only 42% had received formal education on prescribing PPI long-term. Overall, 93% believed they would benefit from such teaching, with 98% stating they would follow related guidelines. No between-group differences were noted in knowledge of appropriate PPI indications nor possible side effects when comparing juniors to seniors, or among different specialties. Across different management scenarios, inappropriate PPI discontinuation was chosen by 14.3% to 67.2%, whereas inappropriate PPI continuation was reported in up to 57%. Trainee seniority and specialty did not differ in appropriate deprescribing rates. CONCLUSIONS: Training level and primary versus specialty care settings are associated with frequent inappropriate PPI prescribing and deprescribing. These findings highlight the need for and may inform future educational programs on PPI usage.

Review article: Advances in the management of lower gastrointestinal bleeding.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is a common emergency with substantial associated morbidity and mortality. Elective colonoscopy plays an essential role in management, with an even more important role for radiology in the acute setting. Recent advances in the management of patients with LGIB warrant review as the management has recently evolved. AIMS: To provide a comprehensive and updated overview of advances in the approach to patients with LGIB METHODS: We performed a comprehensive literature search to examine the current data for this narrative review supplemented by expert opinion. RESULTS: The incidence of LGIB is increasing worldwide, partly related to an ageing population and the increasing use of antithrombotics. Diverticulosis continues to be the most common aetiology of LGIB. Pre-endoscopic risk stratification tools, especially the Oakland score, can aid appropriate patient triage. Adequate resuscitation continues to form the basis of management, while appropriate management of antithrombotics is crucial to balance the risk of worsening bleeding against increased cardiovascular risk. Radiological imaging plays an essential role in the diagnosis and treatment of acute LGIB, especially among unstable patients. Colonoscopy remains the gold-standard test for the elective management of stable patients. CONCLUSIONS: The management of LGIB has evolved significantly in recent years, with a shift towards radiological interventions for unstable patients while reserving elective colonoscopy for stable patients. A multidisciplinary approach is essential to optimise the outcomes of patients with LGIB.

Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy.

ABSTRACT: The management of inflammatory bowel disease (IBD) in pregnant women is challenging and must be addressed on a patient-by-patient basis. Optimal patient management requires a multidisciplinary team and clear evidence-based recommendations that cater to this subset of patients. In this article, we provide concise guidelines and clinical care pathway for the management of IBD in pregnant women. Our recommendations were developed by a multidisciplinary working group that includes experts from the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacology. All recommendations are based on up-to-date information following an extensive literature review. A total of 23 evidence-based expert opinion recommendations for the management of IBD in pregnant women are herein provided.

Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease.

Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.

Predictors of Anti-TNF Therapy Failure among Inflammatory Bowel Disease (IBD) Patients in Saudi Arabia: A Single-Center Study.

BACKGROUND: The advent of monoclonal antibodies (mAbs) has revolutionized the management of many immune-mediated diseases such as inflammatory bowel disease (IBD). Infliximab and adalimumab were the first mAbs approved for the management of IBD, and are still commonly prescribed for the treatment of both Crohn's disease (CD) and ulcerative colitis (UC). Although mAbs have demonstrated high effectiveness rates in the management of IBD, some patients fail to respond adequately to mAbs, resulting in disease progression and the flare-up of symptoms. OBJECTIVE: The objective was to explore the predictors of treatment failure among IBD patients on infliximab (INF) and adalimumab (ADA)-as demonstrated via colonoscopy with a simple endoscopic score (SES-CD) of ≥1 for CD and a Mayo score of ≥2 for UC-and compare the rates of treatment failure among patients on those two mAbs. METHODS: This was a prospective cohort study among IBD patients aged 18 years and above who had not had any exposure to mAbs before. Those patients were followed after the initiation of biologic treatment with either INF or ADA until they were switched to another treatment due to failure of these mAbs in preventing the disease progression. Univariate and multiple logistic regressions were conducted to examine the predictors and rates of treatment failure. RESULTS: A total of 146 IBD patients (118 patients on INF and 28 on ADA) met the inclusion criteria and were included in the analysis. The mean age of the patients was 31 years, and most of them were males (59%) with CD (75%). About 27% and 26% of the patients had penetrating and non-stricturing-non-penetrating CD behavior, respectively. Patients with UC had significantly higher odds of treatment failure compared to their counterparts with CD (OR = 2.58, 95% CI [1.06-6.26], p = 0.035). Those with left-sided disease had significantly higher odds of treatment failure (OR = 4.28, 95% CI [1.42-12.81], p = 0.0094). Patients on ADA had higher odds of treatment failure in comparison to those on INF (OR = 26.91, 95% CI [7.75-93.39], p = 0.0001). CONCLUSION: Infliximab was shown to be more effective in the management of IBD, with lower incidence rates of treatment failure in comparison to adalimumab.

Early cholangioscopy-assisted electrohydraulic lithotripsy in difficult biliary stones is cost-effective.

BACKGROUND AND AIMS: Single-operator cholangioscopy-assisted electrohydraulic lithotripsy (SOC-EHL) is effective and safe in difficult choledocholithiasis. The optimal timing of SOC-EHL use, however, in refractory stones has not been elucidated. The following aims to determine the most cost-effective timing of SOC-EHL introduction in the management of choledocholithiasis. METHODS: A cost-effectiveness model was developed assessing three strategies with a progressively delayed introduction of SOC-EHL. Probability estimates of patient pathways were obtained from a systematic review. The unit of effectiveness is complete ductal clearance without need for surgery. Cost is expressed in 2018 US dollars and stem from outpatient US databases. RESULTS: The three strategies achieved comparable ductal clearance rates ranging from 97.3% to 99.7%. The least expensive strategy is to perform SOC-EHL during the first endoscopic retrograde cholangiography pancreatography (ERCP) (SOC-1: 18,506$). The strategy of postponing the use of SOC-EHL to the third ERCP (SOC-3) is more expensive (US$18,895) but is 2% more effective. (0.9967). SOC-EHL during the second ERCP in the model (SOC-2) is the least cost-effective. Sensitivity analyses show altered conclusions according to the cost of SOC-EHL, effectiveness of conventional ERCP, and altered willingness-to-pay (WTP) thresholds with early SOC-1 being the most optimal approach below a WTP cut-off of US$20,295. CONCLUSIONS: Early utilization of SOC-EHL (SOC-1) in difficult choledocholithiasis may be the least costly strategy with an effectiveness approximating those achieved with a delayed approach where one or more conventional ERCP(s) are reattempted prior to SOC-EHL introduction.

Association of HER1 and HER2 Gene Variants in the Predisposition of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. OBJECTIVE: In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. METHODS: TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. RESULTS: In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. CONCLUSIONS: Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.

Prevalence, severity and associated factors of restless leg syndrome in inflammatory bowel disease patients.

BACKGROUND: The association between restless leg syndrome (RLS) and inflammatory bowel disease (IBD) has often been an under-investigated and clinically misdiagnosed entity. An emphasis should be made on the severity and associated factors, as the prevalence of both entities is on the rise globally. In this study we aimed to investigate the prevalence, severity and associated risk factors of RLS in patients with IBD. METHODS: A multi-center, prospective cross-sectional study was conducted with age and gender matched controls in the ratio of 1:3. Cases of IBD were confirmed according to European Crohns and Colitis Organization guidelines. The study recruited 377 cases and 1131 age and gender-matched controls. RLS severity and prevalence was determined using a validated International Restless Legs Syndrome Study Group questionnaire. The anthropometric and blood biochemical measurements were retrieved from the patient's medical records. Associated factors were analyzed by regression analysis. RESULTS: The prevalence of RLS in patients with IBD and non-IBD control groups was 21.5% and 9.7%, respectively (P = 0.001). The severity index of RLS symptoms in all the three categories of mild, moderate and severe RLS was higher in the IBD group (P = 0.001). Obesity (BMI >30 Kg/m2) was more prevalent in patients with IBD with RLS than without RLS (21.9%: 10.3%, P = 0.009). Ages between 46 and 59 years (OR = 18.7 [2.6-29.4], P = 0.008), obesity (OR = 22 [2.6-29.4], P = 0.005), higher TSH levels (OR = 1.7 [1.0-3.0], P = 0.033), and lower hemoglobin levels (P = 0.028) showed a greater risk associated with RLS. CONCLUSION: Prevalence and severity of RLS was higher in patients with IBD. The risk factors for RLS in IBD include increasing age, obesity, higher TSH, and lower hemoglobin.

Use of stents in patients undergoing chemotherapy for borderline resectable pancreatic cancer-causing biliary obstruction while awaiting surgery: A cost-effectiveness analysis.

Background and study aims Biliary stenting is indicated to relieve obstruction from borderline resectable pancreatic cancer while patients receive preoperative neoadjuvant therapy. We compared the cost-effectiveness of plastic versus metal biliary stenting in this setting. Methods A decision tree analysis compares two competing types of biliary stents (initially metal vs. initially plastic) to treat malignant distal biliary obstruction while receiving neoadjuvant therapy with different scenarios including possible complications as bridge till the patient undergoes curative surgical attempt. Using published information, effectiveness was chosen as the probability of successfully reaching a state of being ready for surgery once chemotherapy was completed. Costs (2018 US$) were based on national data. A third-party payer perspective was adopted, and sensitivity analyses were performed over a time-horizon of one year. Results Initially inserting a metal versus a plastic biliary stent was more efficacious with a higher probability of reaching the readiness for surgery endpoint (96 % vs. 85 %), on average 18 days earlier while also being less expensive (US$ 9,304 vs. US$ 11,538). Sensitivity analyses confirmed robustness of these results across varying probability assumptions of plausible ranges and remained a dominant strategy even when lowering the willingness-to-pay threshold to US$ 1,000. Conclusions Initial metal stenting to relieve malignant biliary obstruction from borderline resectable pancreatic cancer in patients undergoing neoadjuvant therapy prior to surgery is a dominant intervention in economic terms, when compared to initially inserting a plastic biliary stent as it results in a greater proportion of patients being fit for surgery earlier and at a lower cost.

Expression and Polymorphism of TSLP/TSLP Receptors as Potential Diagnostic Markers of Colorectal Cancer Progression.

Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study.

OBJECTIVE: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). DESIGN: Prospective cohort study. SETTING: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES: The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. CONCLUSIONS: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. STUDY REGISTRATION: ClinicalTrials.gov NCT03225586.