Gastrointestinal Tract

Safety outcomes of low versus high dose imatinib mesylate in patients with advanced, metastatic, or nonresectable gastrointestinal stromal tumors: A systematic review

Marena A. Marucci — 2024-03-12

Background and Objectives: Gastrointestinal stromal tumors (GIST) are a rare cancer where tumors grow along the gastrointestinal tract. While treatment options aim towards surgical resection, some patients present with advanced metastatic and/or nonresectable diseases. The tyrosine kinase inhibitor imatinib mesylate is approved for this indication. However, dose escalation from 400 to 600 mg/d or 800 mg/d is allowed. The present study systematically evaluates the safety outcomes, particularly the incidence of grade ≥ 3 adverse events (AEs) with low dose compared with high dose imatinib in these patients. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines were utilized to identify relevant studies through the PubMed, Cochrane Library, and Ovid databases and included randomized and non-randomized clinical trials comparing a low dose intervention of imatinib 400 mg/d with a high dose comparator of 600 or 800 mg/d in patients with histologically confirmed advanced metastatic and/or nonresectable GIST. Four studies were reviewed regarding study summaries and patient characteristics, patient demographics, and risk of bias, with a main emphasis on the evaluation of both efficacy outcomes and safety outcomes. Results: Three of the four studies did not provide significant differences in response outcomes; however, all four studies reported a higher incidence of grade ≥ 3 AEs in the high dose imatinib groups. Individual study reports of more high dose patients experiencing a grade ≥ 3 event ranged from 0.6% to 19.8%, while combined low and high dose patient arms revealed a 17.1% difference favoring a high dose patient event. A sub-analysis of the three most frequently occurring categories, blood and lymphatic system disorders, gastrointestinal disorders, and general disorders and administration site conditions each revealed more high dose patients experiencing said category events compared to those low dose counterparts. Conclusion: Low dose imatinib provides clinically meaningful response and demonstrated better tolerability with less frequently reported reactions. This evidence supports further research into the maintenance of 400 mg/d for this patient population compared to a dose
escalation.

Multi-modal conservative management of intra-abdominal collections in fistulising Crohn’s disease

Mohammad Shir Ali — 2024-02-22

Background and Objectives: The management of intra-abdominal collections in fistulising Crohn’s disease (CD) has traditionally involved surgery. However, conservative management is a potential alternative. In this study, we report our experience with multi-modal conservative management of intra-abdominal collections secondary to perforating CD. Methods: Medical records of CD patients with a history of intra-abdominal collections or fistulas over the past five years were reviewed retrospectively. Patients were included if they were initially managed conservatively using any combination of antibiotics, exclusive enteral nutrition (EEN), percutaneous drainage of collections, endoscopic dilatation of associated strictures and medical therapy for IBD with steroids, immunomodulators and/or biologics. Results: Eleven participants were included. All participants had penetrating CD affecting the terminal ileum. Nine participants had intra-abdominal collection on cross-sectional imaging whilst the remaining two participants had fistulising disease and sepsis without a discrete collection. Eight participants completed a 6–8 weeks course of EEN. All participants were treated with antibiotics and a thiopurine. Steroids were used in eight participants and biological agents in six. Six participants underwent endoscopic dilatation of small bowel strictures. After a median follow up of 20 months [range: 3–210] nine participants had evidence of adequate clinical, biochemical, radiological and endoscopic improvement. Complete resolution of abscess was seen in 4/7 participants and a significant reduction in abscess size was seen in 2/7. Two participants had complete endoscopic and histological remission and complete resolution of abscess. Both participants with fistulising disease (without a collection) had evidence of healed fistula tract on progress imaging and endoscopy. Two participants underwent surgery after failure of initial conservative management. Conclusion: Intra-abdominal collections in fistulising CD can be managed successfully in appropriately selected patients using a multi-modal approach incorporating antibiotics, EEN, endoscopic dilatations of culprit strictures and optimised medical management using steroids (for induction of remission), immunomodulators and biologics.