Anusha Shirwaikar Thomas

Objectives: Many patients with cancer receive chemotherapy alongside glucagon-like peptide-1 receptor agonists (GLP-1 RA) to manage type 2 diabetes or obesity. However, both GLP-1 RA and platinum-based chemotherapies can cause upper gastrointestinal (GI) adverse effects (AE) such as nausea and vomiting. This study aimed to evaluate the impact of GLP-1 RA use in patients receiving platinum-based chemotherapy, focusing on GI AE incidence, risk factors, and treatment outcomes. Methods: This single-center study retrospectively reviewed patients who were treated with a platinum-based therapy and concurrent GLP-1 RA and developed symptoms of upper GI AE. Results: The study included 200 patients. Upper GI adverse events occurred in 126 patients. Compared with patients without GI AE, patients with GI AE received fewer doses of platinum therapy (median: 2.5 vs. 5, P P =0.034), shorter follow-up (median: 1.5 vs. 2.7 y, P P =0.025). GI AEs were treated with 5-HT3 receptor antagonists in 123 (99.2%) patients and corticosteroids in 5 (4.0%). GI AE symptoms lasted a median of 42.5 days; 92.7% achieved clinical remission of GI AE. Twenty-one (16.7%) patients required hospitalization for GI AE, of whom 4 required rehospitalization. Platinum analogs were discontinued in 72 (57.1%) patients and resumed in 57 (79.2%). GLP-1 RA was discontinued in 11 (8.7%) patients. Conclusions: Most patients receiving GLP-1 RA and platinum-based chemotherapy developed mild GI AE that responded to conservative management.

Background/Objective: Immune checkpoint inhibitors (ICIs) are highly effective cancer therapies used across a broad spectrum of malignancies. They function by disrupting immune inhibitory pathways, resulting in an amplified immune response against tumors. However, this heightened immune activity can predispose patients to immune-mediated colitis (IMC), which is graded using the Common Terminology Criteria for Adverse Events (CTCAE) and can range from mild diarrhea to severe colitis. Prior studies have shown that fecal stream diversion can modify the gut microbiome and influence the severity of intestinal inflammation. This study investigates the impact of fecal stream diversion on IMC outcomes in cancer patients receiving ICIs. Methods: We conducted a retrospective cohort study of patients treated with ICIs from 2016 to 2023 who had a history of fecal stream diversion. Demographic, oncologic, and toxicity-related data were collected. Patients with active gastrointestinal infections, autoimmune GI diseases, or graft-versus-host disease were excluded. Descriptive statistics and univariate and multivariate logistic regression analyses were performed using SAS version 9.4. Results: A total of 44 patients were included and categorized into two groups based on the timing of bowel stoma creation relative to the IMC event. CTCAE grade for diarrhea was used to assess GI toxicity. While overall CTCAE grade distribution for diarrhea did not differ significantly between groups (p = 0.22), Hispanic ethnicity was significantly associated with a lower CTCAE grade compared to non-Hispanic or Latino individuals (OR [95% CI] = 0.12 [0.02, 0.62], p = 0.011). In contrast, higher CTCAE grades were significantly associated with ileostomy versus colostomy (OR [95% CI] = 3.21 [1.01, 10.18], p = 0.048) and in patients without an ostomy at the time of diarrhea onset compared to those with an ostomy (OR [95% CI] = 8.87 [2.51, 31.31], p = 0.0007). Conclusions: Our findings suggest that the CTCAE diarrhea grade is significantly associated with ethnicity, type of stoma, and presence of ostomy at the time of diarrhea. Limitations include the retrospective study design and small sample size. These results contribute to understanding potential strategies for mitigating the serious gastrointestinal toxicities of ICIs.

Autoimmune pancreatitis is a rare condition of pancreatic inflammation with two classic subtypes. The emergence of a third subtype, ICI-induced pancreatitis, highlights the need for knowledge of each type to ensure accurate diagnosis and treatment. Abbreviations: AIP—Autoimmune pancreatitis; AIP-1—Type 1 autoimmune pancreatitis, also known as lymphoplasmacytic sclerosing pancreatitis (LPSP); AIP-2—Type 2 autoimmune pancreatitis, also referred to as idiopathic duct-centric pancreatitis (IDCP); AIP-3—Type 3 autoimmune pancreatitis, also known as immune checkpoint inhibitor (ICI)-induced autoimmune pancreatitis; IgG4-RD—Immunoglobulin G4-related disease.

Gastrointestinal homeostasis describes a delicate state of equilibrium in which various systems cooperate to maintain digestive health, support microbial activity, and regulate immune responses. There is growing evidence that Vitamin D is one of the many factors that influences gastrointestinal homeostasis through its effects on gut barrier integrity, regulating microbial diversity and modulating immune responses. Given these effects of Vitamin D, there may be potential for it as both a preventative and a therapeutic intervention for a variety of conditions, but especially for inflammatory conditions of the gastrointestinal tract. This article will summarize the role of Vitamin D in a state of equilibrium, as well as its role in a pro-inflammatory state in the gastrointestinal tract.