after Lower Endoscopy Supervisor 邱宗傑 主任 Presented by 郭政裕 總醫師 NEJM Sep 19 2013 PolypCancer sequency Morphology Anatomic Distribution and Cancer Potential of Colonic Polyps Annals Surgery ID: 920735
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Slide1
Long-Term Colorectal-Cancer Incidence and Mortality after Lower Endoscopy
Supervisor: 邱宗傑 主任Presented by 郭政裕 總醫師
NEJM
, Sep 19, 2013
Slide2Polyp-Cancer sequency
?
Slide3Slide4Morphology, Anatomic Distribution and Cancer Potential of Colonic Polyps. Annals Surgery
1979;190:679-683.
Slide5Morphology, Anatomic Distribution and Cancer Potential of Colonic Polyps. Annals Surgery
1979;190:679-683.
Slide6Familiar adenomatous polyposis
(FAP)
APC
mutations (
Adenomatous
polyposis
coli
)
An
inherited cancer-predisposition
syndrome
more than 100
adenomatous
polyps
in
carriers of the
mutant
gene
, the risk of colorectal cancer by the age of 40 years is almost 100%
Kathleen H. Biology Of The
APC
Tumor Suppressor
. J
Clin
Oncol
2000;18:1967-1979
.
Slide7Slide8Animal model:
The Apcmin mouse
chemical mutagenesis that
introduced a chain-terminating mutation at
nucleotide 2549
in
mApc
develop
numerous intestinal adenomas
in which
the remaining wild-type allele is somatically
inactivated
during adenoma development
Kathleen H. Biology Of The
APC
Tumor Suppressor
. J
Clin
Oncol
2000;18:1967-1979
.
Slide9Sporadic colorectal adenoma and cancers
APC Somatic mutations and deletions that inactivate both copies of APC
are present in most patients
Wild-type
APC
Mutations of β-
catenin
resistent
to the
β-
catenin
degradation complex
Kathleen H. Biology Of The
APC
Tumor Suppressor
. J
Clin
Oncol
2000;18:1967-1979
.
Slide10Sanford D.
Moleucular
Basis of Colorectal Cancer. N
Engl
J Med 2009;361:2449-60.
Slide11Sanford D.
Moleucular
Basis of Colorectal Cancer. N
Engl
J Med 2009;361:2449-60.
Slide12Slide13Methods
Study populationProspective cohort studyThe Nurses’ Health Study: 121,700 U.S. female nurses (30~55 y/o), since 1976The Health Professionals Follow-up Study: 51,529 U.S. male health professionals (40~75 y/o),
sinc
1986
Exclusion criteria
History of cancer
Ulcerative colitis
Colorectal polyps
Familiar
polyposis
syndromes
Previous lower endoscopy
Slide14Observational studies
Enrolled: n=88,902 (31,736 men, 57,166 women)1998~2008Questionnaire and collect information every 2 year (Low GI endoscopy: sigmoidscopy or colonoscopy) Incidence analysis in 2010, mortality analysis in 2012
Slide15Polyps
Adenomatous polyps Advanced adenoma (≥10 mm, tubulovillus or villous, or high-grade dysplasia)
High-risk adenoma ( numbers ≥ 3)
Colonoscopic
polypectomy
: excision of
comfirmed
adenomatous
polyps (excluding
hyperplastic
polyps)
Negative endoscopy: no adenomas or
CRCs
Slide16Molecular analysis
Microsatellite instability statusBRAF (codon 600)KRAS (
codon
12 and 13)
PIK3CA
(
exons
9 and 20)
DNA
methylation
(8
CpG
island
methylator
phenotype,
CIMP
)
Specific
promotors
:
MLH1
,
CACNA1G
,
CDKN2A
, CRABP1, IGF2, NEUROG1, RUNX3, and SOCS1)Long interspersed nucleotide element 1 (LINE-1)
Slide17Slide18Results88,902 participants, follow-up for 22 years
Received endoscopy vs. without endoscopyColorectal cancer: 1815 incident cases (2%)
Slide19Slide20Slide21Screen colonscopy interval
Slide22Surveillance colonoscopy interval after removal of adenomatous polyps
Slide23Slide24Slide25Slide26Summary
Low gastrointestinal endoscopy is associated with a low incidence and low mortality of colorectal cancerTumor molecular features of the serrated pathway might be involved in the development of cancer within
5
years after colonoscopy
Slide27Thanks for your attention!