Review Reports

Round 1

Reviewer 1 Report

The gene-based management for Lynch Syndrome is advocated in many studies, and society guidelines have started to adopted this view, European and US guidelines now advocating genotype-based surveillance and management. This manuscript of a short review now utilizes this view.

 

The manuscript states that ”data on the impact of sigmoid colon preservation on oncologic outcomes and quality of life is lacking”, and that “Reports on the rate of metachronous cancer in CRC patients with LS after subtotal colectomy with ileorectal or ileosigmoid anastomosis are lacking”. 

 

These statements are not entirely accurate, as reference 18 shows that the risk of metachronous CRC is greatly reduced by STC+ISA compared to segmental resection (not included in the meta-analyses). The functional outcomes from ISA compared to IRA show benefit for ISA, although the immediate postoperative bowel movements take a bit longer time, and the anastomotic leakage rate for ISA is substantially lower than for IRA (https://pubmed.ncbi.nlm.nih.gov/18470560/ , https://pubmed.ncbi.nlm.nih.gov/24428330/ , https://pubmed.ncbi.nlm.nih.gov/29059489/). There is physiological rationale for sparing the rectosigmoid area of the colorectum, that is responsible for most of the functional performance (rectosigmoid break, https://pubmed.ncbi.nlm.nih.gov/28419527/ , https://pubmed.ncbi.nlm.nih.gov/28336544/ , https://www.medrxiv.org/content/10.1101/2021.11.30.21266844v2.full ) Especially the risk of morbidity related to IRA should be acknowledged in the review.

 

It seems clear by now that endoscopic surveillance does not greatly reduce the incidence of CRC, which could be highlighted as the most prominent rationale for extended surgery.

 

Ileocecal anastomosis is a typo (r 142).

 

As far as I’m aware of, there is no compelling original evidence in reference 31 or elsewhere to show that the survival would be improved by STC compared to segmental resection, so I would suggest to omit this statement (r 177).

 

References 7 and 24 are the same paper.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Dear Author,

 

This is a review article about metachronous colorectal cancer in Lynch syndrome.

I think this article will give readers robust overview about Lynch syndrome since the important studies are appropriately cited and the information is clearly demonstrated. However, guidelines about Lynch syndrome had already been published from many groups. (1-4) Therefore, it seems difficult to me to find the specific meaning of this article.

 

 There is a subtle mistake in page 4 line 142, “ileocecal anastomosis” should be “ileosigmoidal/ileorectal anastomosis”.

 

Regards,

 

1.           Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut. 2020;69(3):411-44.

2.           Seppälä TT, Latchford A, Negoi I, Sampaio Soares A, Jimenez-Rodriguez R, Sánchez-Guillén L, et al. European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. Br J Surg. 2021;108(5):484-98.

3.           Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. The American journal of gastroenterology. 2015;110(2):223-62; quiz 63.

4.           Tomita N, Ishida H, Tanakaya K, Yamaguchi T, Kumamoto K, Tanaka T, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer. International journal of clinical oncology. 2021;26(8):1353-419.

 

Author Response

Dear reviewer,

 

thank you very much for reviewing this article. I agree with you that the article has some redundancy to available guidelines. Many published guidelines discuss several aspects of the management of Lynch Syndrome including surveillance, medical treatment, etc. This review intended to specifically discuss the surgical options in Lynch syndrome carriers for an audience that is looking for a concise overview of surgical strategies in LS. I believe therefore that it has its place for readers looking specifically for that.

Thank you for pointing out the typo. I have corrected it.

Round 2

Reviewer 2 Report

Dear Author,

 

Thank you for your revision.

I understood that this manuscript was focused on the surgical aspects of treatment for LS. I’m impressed with the rewritten part that described preferable points (quality of life and anastomotic leakage rate) of subtotal colectomy with ileosigmoidal anastomosis rather than ileorectal anastomosis in response to the reviewer 1. I’m afraid that part (written in the authors’ response to reviewer 1) is missing from the revised manuscript.

 

Regards,

Author Response

Dear reviewer,

thank you very much for taking the time to review the manuscript again and pointing out the missing part. The versions must have gotten confused somehow. I have now resubmitted the latest version including the missing parts.

Kind regards