Bryan P Kline1, Kathleen M Schieffer1, Christine S Choi1, Tara Connelly1, Jeffrey Chen2, Leonard Harris1, Sue Deiling1, Gregory S Yochum1,3, Walter A Koltun4. 1. Division of Colon and Rectal Surgery, Department of Surgery, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, 17033-0850, USA. 2. Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA. 3. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA. 4. Division of Colon and Rectal Surgery, Department of Surgery, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, 17033-0850, USA. wkoltun@pennstatehealth.psu.edu.
Abstract
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.
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.
Entities:
Keywords:
Diverticular disease; Diverticulitis; RNA-seq; Recurrence; Surgery
Authors: Daniel Feingold; Scott R Steele; Sang Lee; Andreas Kaiser; Robin Boushey; W Donald Buie; Janice Frederick Rafferty Journal: Dis Colon Rectum Date: 2014-03 Impact factor: 4.585
Authors: A Izadpanah; M B Dwinell; L Eckmann; N M Varki; M F Kagnoff Journal: Am J Physiol Gastrointest Liver Physiol Date: 2001-04 Impact factor: 4.052
Authors: Tara M Connelly; Arthur S Berg; John P Hegarty; Sue Deiling; David Brinton; Lisa S Poritz; Walter A Koltun Journal: Ann Surg Date: 2014-06 Impact factor: 12.969
Authors: Enis Afgan; Dannon Baker; Marius van den Beek; Daniel Blankenberg; Dave Bouvier; Martin Čech; John Chilton; Dave Clements; Nate Coraor; Carl Eberhard; Björn Grüning; Aysam Guerler; Jennifer Hillman-Jackson; Greg Von Kuster; Eric Rasche; Nicola Soranzo; Nitesh Turaga; James Taylor; Anton Nekrutenko; Jeremy Goecks Journal: Nucleic Acids Res Date: 2016-05-02 Impact factor: 16.971
Authors: Snaevar Sigurdsson; Kristjan F Alexandersson; Patrick Sulem; Bjarke Feenstra; Steinunn Gudmundsdottir; Gisli H Halldorsson; Sigurgeir Olafsson; Asgeir Sigurdsson; Thorunn Rafnar; Thorgeir Thorgeirsson; Erik Sørensen; Andreas Nordholm-Carstensen; Jakob Burcharth; Jens Andersen; Henrik Stig Jørgensen; Emma Possfelt-Møller; Henrik Ullum; Gudmar Thorleifsson; Gisli Masson; Unnur Thorsteinsdottir; Mads Melbye; Daniel F Gudbjartsson; Tryggvi Stefansson; Ingileif Jonsdottir; Kari Stefansson Journal: Nat Commun Date: 2017-06-06 Impact factor: 14.919