P0323 - Twists and Turns: Small Bowel Enteritis as an Unusual Consequence of 5-FU Toxicity in the Setting of DPD Deficiency

Harman Sawhney, DO¹, Phillip Hall, MD¹, Kovil Ramasamy, MD², Dhanush Hoskere, DO^1
1Bayonne Medical Center, Bayonne, NJ; ²CarePoint Health - Bayonne Medical Center, Bayonne, NJ

Introduction: Dihydropyrimidine Dehydrogenase (DPD) deficiency is a rare genetic disorder that affects one's ability to metabolize fluoropyrimidine medications. 5-Flurouracil (5-FU) is an agent that is commonly used in the treatment of colorectal cancers. DPD is an enzyme that metabolizes 5-FU into inactive metabolites to be safely excreted from the body. It is established that diarrhea and mucositis are common adverse effects of 5-FU. However, life threatening enteritis in the setting of DPD deficiency and the role of DPD genetic testing before 5-FU administration is starting to become more recognized.

Case Description/Methods: 71 year old male who presented with abdominal pain. He admitted to unintentional weight loss over the past 10 years. Colonoscopy 8 years prior was benign. CTAP showed cecal thickening with a possible mass. An inpatient colonoscopy showed a cecal mass positive for adenocarcinoma. He was taken for a successful right hemi-colectomy and was started on 5-FU in the outpatient setting.

5 months later, he returned with fever, abdominal pain, and nausea. CTAP showed worsening of small bowel dilation and moderate dilation of a fluid-filled colon and rectum without any signs of obstruction; Findings could be related to nonspecific infections/inflammatory enteritis and colitis/diarrhea. Despite antibiotic treatment and naso-gastric tube placement for suspected ileus, the patient's symptoms did not improve. Repeat CTAP showed a large amount of fluid in the cecum/ascending/proximal transverse colon and left colon; Thickening of the distal descending and sigmoid colon was noted. The patient eventually recovered and was subsequently started on Bifidobacterium probiotic supplementation. He was found to have DPD deficiency.

Discussion: Identification of DPD deficiency before initiating 5-FU treatment is now becoming more standard of care. Methods including genetic testing and enzyme activity assays can be utilized to assess DPD functioning. The incidence of severe 5-FU toxicity such as enteritis in individuals with DPD deficiency has been estimated to be around 10-30%. The European Medicines Agency advises standardized testing for DPD deficiency before starting systemic therapy with 5-FU or similar medicines. Hematology/Oncology viewpoints accord with the EMA and medical organizations, emphasizing the need of DPD testing to reduce the risk of adverse responses to 5-FU. Testing gives critical information for personalized treatment strategies and improves patient safety.


Disclosures:


Harman Sawhney, DO¹, Phillip Hall, MD¹, Kovil Ramasamy, MD², Dhanush Hoskere, DO¹. P0323 - Twists and Turns: Small Bowel Enteritis as an Unusual Consequence of 5-FU Toxicity in the Setting of DPD Deficiency, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.