pathology of tumours of the lower gastrointestinal tract...pathology of tumours of the lower...
TRANSCRIPT
-
pathology of tumours of the lower gastrointestinal
tract
Dr Simon CrossAcademic Unit of Pathology
University of Sheffield
adenomas
colorectal cancer
0
1,000
2,000
3,000
4,000
0-4
5-9
10-1
4
15-1
9
20-2
4
25-2
9
30-3
4
35-3
9
40-4
4
45-4
9
50-5
4
55-5
9
60-6
4
65-6
9
70-7
4
75-7
9
80-8
4
85+
Age at diagnosis
Nu
mb
er
of
cases
0
200
400
600
Ra
te p
er
10
0,0
00
po
pu
lati
on
Male cases
Female cases
Male rates
Female rates
New cases and age-specific incidence rates - bowel cancer, UK 2005
3
Incidence rates - world regions, 2002 estimates
0 5 10 15 20 25 30 35 40 45 50
Middle Africa
South-central Asia
Northern Africa
Western Africa
Eastern Africa
Central America
Melanesia
Western Asia
Southern Africa
South-Eastern Asia
China
Polynesia
Caribbean
Micronesia
South America
Eastern Asia
Central & Eastern Europe
Southern Europe
Northern Europe
Western Europe
Northern America
Australia/New Zealand
Rate per 100,000 population
Males
Females
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
1975
1977
1979
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
Year of diagnosis/death
Rate
per
100,0
00 p
op
ula
tio
n
Incidence males Incidence females
Mortality males Mortality females
Incidence and mortality rates - colorectal cancer, Great Britain, 1975-2005
5
who gets colorectal cancer?
-
normal epithelium
dysplastic epithelium
-
normalepithelium
adenomacolorectal
adenocarcinoma
familial adenomatous
polyposis
Polyps
nucleus
nuclear membrane
DNA
cytoplasmapcGSK
betacatenin
-
apcGSK
betacatenin
apcGSK
betacatenin
apc
apcGSK
betacatenin
epithelialproliferation
adenoma
apcGSK
betacatenin
apcGSK
betacatenin
apcGSK
betacatenin
-
apcGSK
betacatenin
epithelialproliferation
adenoma
hereditary nonpolyposis colorectal cancer
HNPCC
DNA repairprotein gene
DNA repairprotein gene1st hit
2nd hit
no DNA repair protein produced
reasons for identifying HNPCC cancers
• risk of further cancers in index patient and relatives
• possible implications for therapy– tolerance of 5-FU etc.– do not recognise DNA damage– apoptosis not activated
-
macroscopic features of colorectal cancer
31
Figure 1.1: Percentage distribution of cases by site within the large bowel, England 1997-2000
38%
colorectal cancer - microscopic
• adenocarcinoma
colorectal cancerstaging & prognosis
-
Posterior view of total
mesorectal excision of
rectal cancer
Anterior view of total
mesorectal excision of
rectal cancer
Transverse slices of
specimen Rectal cancer
Rectal cancerInvolved lymph node
-
resection marginscolon
mesentery
-
resection coding
• R0 - tumour completely excised locally• R1 - microscopic involvement of margin by
tumour• R2 - macroscopic involvement of margin by
tumour
prognosis and circumferential resection margin (CRM)
• CRM +ve 20% 5 year survival with 85% risk of local recurrence
• CRM –ve 75% 5 year survival with 10% risk of local recurrence
why stage?
-
mucosamuscularis mucosa
submucosa
muscularis propria
lymph nodes
high tie lymph node
-
Dukes’ pTispN0
Dukes’ A pT1pN0 Dukes’ A pT1pN0
Dukes’ A pT2pN0 Dukes’ B pT3pN0
-
Dukes’ B pT3pN0 Dukes’ C1 pT3pN1
Dukes’ C1 pT3pN1 Dukes’ C2 pT3pN2
Dukes’ A pT2 Dukes’ B pT3
-
mucosa
submucosa
muscularis propria
lymph nodes
serosal/peritoneal surface
Dukes’ B pT3 Dukes’ B pT4
Dukes’ B pT4 Dukes’ B pT4
-
Dukes’ B pT4
Dukes’ stage and prognosis
• A 95% 5 year survival• B 75% 5 year survival• C 35% 5 year survival• D 25% 5 year survival
normalepithelium adenoma
colorectaladenocarcinoma
metastaticcolorectal
adenocarcinoma
endoscopic resection
surgical resection
chemotherapy palliative care
prevention