Background: The management of diverticulitis is compromised by difficulty in identifying patients who require surgery for recurrent or persistent disease. Here, we introduce the concept of multifocal diverticulitis (MFD), characterized by multiple episodes of diverticulitis occurring at different locations within the colon. Aims: To compare clinical characteristics, success of surgical management, and colonic transcriptomes of MFD patients to patients with conventional unifocal diverticulitis (UFD). Methods: This retrospective study included 404 patients with CT-confirmed diverticulitis episodes. Patients with diverticulitis seen in at least two different colonic locations were classified as the MFD group and compared to the UFD group based on number of episodes, sites of disease, family history, surgeries performed, and postoperative recurrence. RNA-seq was conducted on full-thickness colonic tissues of ten MFD and 11 UFD patients. Results: Twenty-eight patients (6.9%) with MFD were identified. MFD patients had more diverticulitis episodes and were more likely to have positive family history, have right-sided disease, require surgery, and have recurrence after surgery. All MFD patients treated with segmental resection had recurrence, while recurrence was less common in patients undergoing more extensive surgery (P < 0.001). Using RNA-seq, we identified 69 genes that were differentially expressed between MFD and UFD patients. Significantly down-regulated genes were associated with immune response pathways. Conclusions: MFD appears to be a more severe subset of diverticulitis with a possible genetic component. Transcriptomic data suggest that MFD may be associated with alteration of the immune response.
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