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Current Issue

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Vascular Surgery, Part I

Vol. 46, No. 6, 2020

  • Abdominal Aortic Aneurysms
  • Aneurysm Risk Factors
  • Diagnosing Abdominal Aortic Aneurysms
  • Technical Features of Aneurysm Repair
  • Thoracic and Thoracoabdominal Aneurysms
  • Inherited Diseases Leading to Thoracic Aortic Dilation
  • Peripheral Artery Aneurysms
  • Popliteal Artery Aneurysms
  • Visceral Artery Aneurysms
Featured Commentary

The online formats of SRGS include access to What You Should Know (WYSK): commentaries on articles published recently in top medical journals. These commentaries, written by practicing surgeons and other medical experts, focus on the strengths and weaknesses of the research, as well as on the articles' contributions in advancing the field of surgery.

Below is a sample of one of the commentaries published in the current edition of WYSK.


Kordahi MC, Stanaway IB, Avril M, et al. Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer. Cell Host Microbe. 2021;29(10):1589-1598.e6. doi:10.1016/j.chom.2021.08.013

Commentary by: Benjamin D. Shogan, MD, FACS, FASCRS

The role of the intestinal microbiota on the pathogenesis of colorectal cancer (CRC) continues to emerge. Investigations like those performed by Kordahi and colleagues are critical to tease out the interaction of commensal bacteria and host epithelium to promote malignancy. In their elegantly performed work, they first demonstrated that a microbial signature differentiates between sessile serrated polyp (SSP), tubular adenomatous (TAP), and polyp-free (PF) tissues. Culturomics discovered that Bacteroides fragilis was present at a higher frequency in patients with polyps, and bacterial presence promoted pro-inflammatory cytokines. To the authors' and this reader's surprise, the enterotoxigenic strain of B. fragilis (ETBF), which has been correlated with CRC, was only rarely identified in their cohort.1 Instead, nontoxigenic B. fragilis predominated in patients with polyps; these strains were significantly enriched with LPS biosynthesis genes and were able to activate TLR4 inducing local inflammation.

This manuscript suggests a role for nontoxigenic B. fragilis (NTBF) in the development of CRC pathogenesis that has previously been unknown. It lends evidence that many commensal organisms or strains, currently thought to be harmless, likely contribute to carcinogenesis. While NTBF was shown to induce local inflammation, precisely how NTBF contributes to a polyp's progression to cancer remains unknown. As the authors discuss, local inflammation induced by NTBF may enhance colonization with other microbes known to have direct carcinogenic effects, such as pks+ Escherichia coli or Fusobacterium nucleatum. This finding again documents the complex interaction of host and microbe within the tumor microenvironment that contributes to malignancy.

Interestingly, the authors demonstrated no significant differences in B. fragilis between TAP and SSP. The malignant transformation between TAP and SSP is distinct, with TAP progressing via the adenoma-to-carcinoma sequence and SSP via CpG island methylation, leading to the silencing of MMR genes. Not surprisingly, MMR silencing is thought to promote a more rapid malignancy transformation, and SSPs are thought to have a higher rate of invasive carcinoma than conventional adenomas.2 Given these pathological and clinical differences, one would hypothesize that the microenvironment between TAP and SSP would be distinct. In fact, Peters et al. found that the stool microbiota significantly differed in patients with conventional adenomas vs. serrated polyps.3 While the current study showed similarities in B. fragilis between polyp types, it is well known that stool and mucosal microbiota can be significantly different. Whether this accounts for the discrepancy remains to be seen.

Finally, while the science is elegant, one must use caution in overinterpretation. First, the sample size is relatively small, and this needs to be confirmed in a larger cohort. For example, the polyp-free clinical isolates tested for inflammation (Figure 3) were from a single patient. While the strains showed a similar phenotype, certainly isolates from other polyp-free patients need to be tested. Second, it is unknown if the epithelial changes created by the polyp promote colonization of NTBF rather than NTBF promoting polyp progression. While increasing polyp size was associated with colonization of NTBF isolates, it remains to be proven if the tumor or microbe is driving this association.

This manuscript shows how a commensal organism, previously thought of as benign, may participate in promoting CRC carcinogenesis. Further research will uncover if the presence of these microbes can be used as a biomarker for CRC development or if decontamination of them is a novel strategy to decrease the incidence of CRC.

References

  1. Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev. 2009;22(2):349-369. doi:10.1128/CMR.00053-08
  2. Cenaj O, Gibson J, Odze RD. Clinicopathologic and outcome study of sessile serrated adenomas/polyps with serrated versus intestinal dysplasia. Mod Pathol. 2018;31(4):633-642. doi:10.1038/modpathol.2017.169
  3. Peters BA, Dominianni C, Shapiro JA, et al. The gut microbiota in conventional and serrated precursors of colorectal cancer [published correction appears in Microbiome. 2017 Mar 6;5(1):29]. Microbiome. 2016;4(1):69. Published 2016 Dec 30. doi:10.1186/s40168-016-0218-6
Recommended Reading

The SRGS Recommended Reading List is a summary of the most pertinent articles cited in each issue; the editor has carefully selected a group of current, classic, and seminal articles for further study in certain formats of SRGS. The citations below are linked to their abstracts on PubMed, and free full texts are available where indicated.

SRGS has obtained permission from journal publishers to reprint these articles. Copying and distributing these reprints is a violation of our licensing agreement with these publishers and is strictly prohibited.

de Guerre L, Dansey K, Li C, et al. Late outcomes after endovascular and open repair of large abdominal aortic aneurysms. J Vasc Surg. Oct 2021;74(4):1152-1160. doi:10.1016/j.jvs.2021.02.024

This article describes a large database study assessing outcomes of open and endovascular aneurysm repairs. According to their data, outcomes were better for open repairs at five years follow-up.

Beuschel B, Nayfeh T, Kunbaz A, et al. A systematic review and meta-analysis of treatment and natural history of popliteal artery aneurysms. J Vasc Surg. Jan 2022;75(1S):121S-125S e14. doi:10.1016/j.jvs.2021.05.023

This systematic review of the literature included 36 acceptable articles. The data analysis showed that complications of popliteal aneurysms increased with time, suggesting that acceptable risk patients should undergo operative repair early in the course of the disease.

Hossack M, Patel S, Gambardella I, Neequaye S, Antoniou GA, Torella F. Endovascular vs. Medical Management for Uncomplicated Acute and Sub-acute Type B Aortic Dissection: A Meta-analysis. Eur J Vasc Endovasc Surg. May 2020;59(5):794-807. doi:10.1016/j.ejvs.2019.08.003

Hossack and coauthors conducted a systematic review add the literature to determine the merit of medical versus endovascular management of type B thoracic aortic aneurysm dissections. Medical therapy was associated with a significantly reduced stroke risk, but endovascular management was associated with superior aorta-related complication rates.

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