MULTIFOCAL DIVERTICULITIS: A SEVERE SUBSET OF DISEASE WITH DISTINCT CLINICAL AND BIOLOGIC FEATURES
Open Access
- Author:
- Kline, Bryan
- Graduate Program:
- Biomedical Sciences
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- June 11, 2019
- Committee Members:
- Walter Alex Koltun, Thesis Advisor/Co-Advisor
Gregory Steven Yochum, Committee Member
Charles H Lang, Committee Member - Keywords:
- Diverticulitis
diverticulosis
gene expression - Abstract:
- Diverticular disease is characterized by diverticula, or outpouchings in the wall of the colon. Although diverticular disease is common, its pathophysiology is poorly understood. The majority of patients with diverticula remain asymptomatic, but some patients develop inflammation of these diverticula, known as diverticulitis. Diverticulitis is often managed medically and without hospitalization, but it can sometimes result in severe complications and require surgical resection. Due to the poor understanding of the factors contributing to disease progression, it can be difficult to identify patients who require surgery to prevent severe disease. To further evaluate the disease, we identified a subset of patients with multifocal diverticulitis (MFD), or multiple episodes of diverticulitis occurring at different locations within the colon. We hypothesized that these patients would display different clinical and transcriptomic characteristics in comparison to patients with conventional unifocal diverticulitis (UFD). We performed a retrospective study of 404 patients with diverticulitis. Of these patients, 28 had diverticulitis in at least two different colonic locations, and thus were classified as MFD patients. A comparison with the UFD patients found that MFD patients had more episodes, more family history of diverticulitis, more right sided disease, were more likely to require surgery, and were more likely to have recurrence after surgery. Transcriptomic analysis was then performed using RNA-seq on full-thickness colonic tissues of 10 MFD and 11 UFD patients matched for age, sex, BMI, and smoking history. We identified 69 differentially expressed genes and MFD patients displayed down-regulation of immune-associated gene sets. Our study found clinical and biologic features that differentiates MFD from UFD. MFD appears to be a more severe disease with a possible genetic component. RNA-seq demonstrates immune dysregulation in MFD. The identification of this subtype adds information about the disease as well as its pathophysiology and may lead to improved management decisions.