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Multifocal Versus Conventional Unifocal Diverticulitis: A Comparison of Clinical and Transcriptomic Characteristics

  • Bryan P. Kline
  • Kathleen M. Schieffer
  • Christine S. Choi
  • Tara Connelly
  • Jeffrey Chen
  • Leonard Harris
  • Sue Deiling
  • Gregory S. Yochum
  • Walter A. KoltunEmail author
Original Article

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.

Keywords

Diverticulitis Diverticular disease Recurrence Surgery RNA-seq 

Notes

Funding

This research was supported by the Carlino Fund for IBD Research.

Compliance with ethical standards

Conflict of interest

None.

Supplementary material

10620_2018_5403_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 15 kb)

References

  1. 1.
    Stollman N, Raskin JB. Diverticular disease of the colon. Lancet. 2004;363:631–639.CrossRefGoogle Scholar
  2. 2.
    Ferzoco LB, Raptopoulos V, Silen W. Acute diverticulitis. N Engl J Med. 1998;338:1521–1526.CrossRefGoogle Scholar
  3. 3.
    Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143:1179–1187.e1-3.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Simpson J, Scholefield JH, Spiller RC. Pathogenesis of colonic diverticula. Br J Surg. 2002;89:546–554.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Jaung R, Robertson J, Vather R, et al. Changes in the approach to acute diverticulitis. ANZ J Surg. 2015;85:715–719.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Aune D, Sen A, Leitzmann MF, et al. Body mass index and physical activity and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies. Eur J Nutr. 2017;56:2423–2438.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Peery AF, Barrett PR, Park D, et al. A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology. 2012;142:266–272.CrossRefPubMedGoogle Scholar
  8. 8.
    Commane DM, Arasaradnam RP, Mills S, et al. Diet, ageing and genetic factors in the pathogenesis of diverticular disease. World J Gastroenterol. 2009;15:2479–2488.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sigurdsson S, Alexandersson KF, Sulem P, et al. Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis. Nat Commun. 2017;8:15789.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Connelly TM, Berg AS, Hegarty JP, et al. The TNFSF15 gene single nucleotide polymorphism rs7848647 is associated with surgical diverticulitis. Ann Surg. 2014;259:1132–1137.CrossRefGoogle Scholar
  11. 11.
    Vennix S, Morton DG, Hahnloser D, et al. Systematic review of evidence and consensus on diverticulitis: an analysis of national and international guidelines. Colorectal Dis. 2014;16:866–878.CrossRefGoogle Scholar
  12. 12.
    Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284–294.CrossRefGoogle Scholar
  13. 13.
    Schieffer KM, Choi CS, Emrich S, et al. RNA-seq implicates deregulation of the immune system in the pathogenesis of diverticulitis. Am J Physiol Gastrointest Liver Physiol. 2017;313:G277–G284.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Afgan E, Baker D, van den Beek M, et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update. Nucleic Acids Res. 2016;44:W3–W10.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Dobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.CrossRefGoogle Scholar
  16. 16.
    Harrow J, Frankish A, Gonzalez JM, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012;22:1760–1774.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Anders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–169.CrossRefGoogle Scholar
  18. 18.
    Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Plotly Technologies Inc. Collaborative data science. Montréal, QC, 2015. https://plot.ly.
  20. 20.
    de Hoon MJ, Imoto S, Nolan J, et al. Open source clustering software. Bioinformatics. 2004;20:1453–1454.CrossRefPubMedGoogle Scholar
  21. 21.
    Saldanha AJ. Java Treeview—extensible visualization of microarray data. Bioinformatics. 2004;20:3246–3248.CrossRefPubMedGoogle Scholar
  22. 22.
    Kuleshov MV, Jones MR, Rouillard AD, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90–W97.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Li D, Baxter NN, McLeod RS, et al. Evolving practice patterns in the management of acute colonic diverticulitis: a population-based analysis. Dis Colon Rectum. 2014;57:1397–1405.CrossRefPubMedGoogle Scholar
  24. 24.
    Tan JP, Barazanchi AW, Singh PP, et al. Predictors of acute diverticulitis severity: a systematic review. Int J Surg. 2016;26:43–52.CrossRefPubMedGoogle Scholar
  25. 25.
    Aune D, Sen A, Leitzmann MF, et al. Tobacco smoking and the risk of diverticular disease—a systematic review and meta-analysis of prospective studies. Colorectal Dis. 2017;19:621–633.CrossRefPubMedGoogle Scholar
  26. 26.
    Golder M, Ster IC, Babu P, et al. Demographic determinants of risk, colon distribution and density scores of diverticular disease. World J Gastroenterol. 2011;17:1009–1017.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Leigh JE, Judd ES, Waugh JM. Diverticulitis of the colon. Recurrence after apparently adequate segmental resection. Am J Surg. 1962;103:51–54.CrossRefPubMedGoogle Scholar
  28. 28.
    Thaler K, Baig MK, Berho M, et al. Determinants of recurrence after sigmoid resection for uncomplicated diverticulitis. Dis Colon Rectum. 2003;46:385–388.CrossRefPubMedGoogle Scholar
  29. 29.
    Benn PL, Wolff BG, Ilstrup DM. Level of anastomosis and recurrent colonic diverticulitis. Am J Surg. 1986;151:269–271.CrossRefPubMedGoogle Scholar
  30. 30.
    Bergamaschi R, Arnaud JP. Anastomosis level and specimen length in surgery for uncomplicated diverticulitis of the sigmoid. Surg Endosc. 1998;12:1149–1151.CrossRefGoogle Scholar
  31. 31.
    Granlund J, Svensson T, Olen O, et al. The genetic influence on diverticular disease—a twin study. Aliment Pharmacol Ther. 2012;35:1103–1107.Google Scholar
  32. 32.
    Strate LL, Erichsen R, Baron JA, et al. Heritability and familial aggregation of diverticular disease: a population-based study of twins and siblings. Gastroenterology. 2013;144:736–742.e1; quiz e14.CrossRefGoogle Scholar
  33. 33.
    Williams IR. CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Ann N Y Acad Sci. 2006;1072:52–61.CrossRefGoogle Scholar
  34. 34.
    Izadpanah A, Dwinell MB, Eckmann L, et al. Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am J Physiol Gastrointest Liver Physiol. 2001;280:G710–G719.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Bryan P. Kline
    • 1
  • Kathleen M. Schieffer
    • 1
  • Christine S. Choi
    • 1
  • Tara Connelly
    • 1
  • Jeffrey Chen
    • 2
  • Leonard Harris
    • 1
  • Sue Deiling
    • 1
  • Gregory S. Yochum
    • 1
    • 3
  • Walter A. Koltun
    • 1
    Email author
  1. 1.Division of Colon and Rectal Surgery, Department of SurgeryThe Pennsylvania State University, College of MedicineHersheyUSA
  2. 2.Department of RadiologyThe Pennsylvania State University, College of MedicineHersheyUSA
  3. 3.Department of Biochemistry and Molecular BiologyThe Pennsylvania State University, College of MedicineHersheyUSA

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