Risk of Metachronous Colorectal Neoplasm after a Segmental Colectomy in Lynch Syndrome Patients According to Mismatch Repair Gene Status.
Adolescent
Adult
Aged
Child
Cohort Studies
Colectomy
/ methods
Colorectal Neoplasms
/ epidemiology
Colorectal Neoplasms, Hereditary Nonpolyposis
/ surgery
DNA Mismatch Repair
/ genetics
Female
Germ-Line Mutation
Humans
Incidence
Male
Middle Aged
Neoplasms, Second Primary
/ epidemiology
Retrospective Studies
Risk Assessment
Young Adult
Journal
Journal of the American College of Surgeons
ISSN: 1879-1190
Titre abrégé: J Am Coll Surg
Pays: United States
ID NLM: 9431305
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
16
12
2019
accepted:
16
01
2020
pubmed:
3
2
2020
medline:
15
12
2020
entrez:
3
2
2020
Statut:
ppublish
Résumé
Because of increased risk of metachronous colorectal cancer (CRC), all patients with Lynch syndrome (LS) are offered a total colectomy. However, because metachronous CRC rate by mismatch repair (MMR) gene is uncertain, and total colectomy negatively impacts quality of life, it remains unclear whether segmental resection is indicated for lower penetrance MMR genes. We evaluated metachronous CRC incidence according to MMR gene in LS patients who underwent a segmental colectomy. Single-center, retrospective cohort study in patients with an earlier colectomy for CRC and an MMR germline mutation in MLH1, MSH2, MSH6, or PMS2 followed prospectively in a hereditary CRC family registry. All patients underwent surveillance colonoscopy. Metachronous CRC was defined as one detected more than 1 year after index resection. Primary end point was cumulative incidence of metachronous CRC overall and by MMR gene. One hundred and ten patients were included: 35 with MLH1 likely pathogenic/pathogenic (LP/P) variants (32%), 42 MSH2 (38%), 20 MSH6 (18%), and 13 PMS2 (12%). Median follow-up 4.26 years (range 0.53 to 19.92 years). Overall, metachronous CRC developed in 22 patients (20%). At 10-year follow-up, incidence was 12% (95% CI 6% to 23%), with no metachronous CRC detected in patients with a PMS2 or MSH6 LP/P variant. After index segmental resection, metachronous CRC is less likely to develop in LS patients with MSH6 or PMS2 LP/P variant than in MLH1 or MSH2 carriers. Our data support segmental resection and long-term colonoscopic surveillance rather than total colectomy in carefully selected, well-informed LS patients with MSH6 or PMS2 LP/P variant.
Sections du résumé
BACKGROUND
Because of increased risk of metachronous colorectal cancer (CRC), all patients with Lynch syndrome (LS) are offered a total colectomy. However, because metachronous CRC rate by mismatch repair (MMR) gene is uncertain, and total colectomy negatively impacts quality of life, it remains unclear whether segmental resection is indicated for lower penetrance MMR genes. We evaluated metachronous CRC incidence according to MMR gene in LS patients who underwent a segmental colectomy.
STUDY DESIGN
Single-center, retrospective cohort study in patients with an earlier colectomy for CRC and an MMR germline mutation in MLH1, MSH2, MSH6, or PMS2 followed prospectively in a hereditary CRC family registry. All patients underwent surveillance colonoscopy. Metachronous CRC was defined as one detected more than 1 year after index resection. Primary end point was cumulative incidence of metachronous CRC overall and by MMR gene.
RESULTS
One hundred and ten patients were included: 35 with MLH1 likely pathogenic/pathogenic (LP/P) variants (32%), 42 MSH2 (38%), 20 MSH6 (18%), and 13 PMS2 (12%). Median follow-up 4.26 years (range 0.53 to 19.92 years). Overall, metachronous CRC developed in 22 patients (20%). At 10-year follow-up, incidence was 12% (95% CI 6% to 23%), with no metachronous CRC detected in patients with a PMS2 or MSH6 LP/P variant.
CONCLUSIONS
After index segmental resection, metachronous CRC is less likely to develop in LS patients with MSH6 or PMS2 LP/P variant than in MLH1 or MSH2 carriers. Our data support segmental resection and long-term colonoscopic surveillance rather than total colectomy in carefully selected, well-informed LS patients with MSH6 or PMS2 LP/P variant.
Identifiants
pubmed: 32007537
pii: S1072-7515(20)30112-5
doi: 10.1016/j.jamcollsurg.2020.01.005
pmc: PMC7104918
mid: NIHMS1564901
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
669-675Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
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