Transcript A-GC

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Carcinomas of the Alimentary tract
Esophageal Carcinoma (EC)
Gastric Carcinoma (GC) Colorectal Carcinoma (CRC)
Viral hepatitis
Preneoplastic disorders of these three tumors:
EC: >90%-squamous cell carcinomas, <10%-adenocarcinomas.
 preceded by chronic esophagitis ---Squamous epithelial
dysplasia --- intraepithelial neoplasia (carcinoma in situ)---preneoplastic disorder
chronic esophagitis
 Barrett esophagus
(precursor of E-adenocarcinoma )
carcinoma in situ
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chronic esophagitis
Many causes may induce chronic esophagitis
Uremia,
prolonged gastric intubation,
ingestion of corrosive or irritant substances,
radiation, and so on
Morphologic change- on gross:
Mild esophagitis: simple hyperemia, with no
histologic abnormality.
Severe esophagitis: epithelial erosion, or ulceration
into the submucosa.
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chronic esophagitis ( on microscope)
 three histologic features:
① eosinophils, with or without neutrophils,
in the epithelial layer;
② basal zone hyperplasia,
③ elongation of lamina propria papillae.
intraepithelial neutrophils occur in more severe injury.
chronic esophagitis
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 Barrett esophagus: Replacement of esophageal squamousepithelium with gastric epithelium (in book page 218)
Gastroesophageal junction
Normal condition
Barrett esophagus
metaplastic columnar
distal esophagus
(pale pink)
gastric epithelium
(salmon-pink)
stomach
(more lush light brown)
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Preneoplastic disorders (precursor lesions)
GC
1. Atrophic chronic gastritis with mucosal dysplasia
2. Adenoma : true neoplasm
containing dysplastic epithelium
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Preneoplastic disorders
CRC
3. FAP（familial
adenomatous polyposis)---
1. Adenoma (villous adenoma)
2. Ulcerative colitis
(in book page 236)
(in book page 231-234)
(in book p237 )
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Adenomas of colon
Basis on the epithelial architecture, adenomas of colon is
divided into three sub-types.
tubular adenomas (most common)
tubulovillous adenoma (5-10%),
villous adenomas (only 1%)
villous adenoma
 On gross: sessile, velvety or cauliflower-like masses;
 On microscope: frondlike villiform extension of the
mucosa is covered by dysplastic epithelium.
 Invasive carcinoma is found in up to 40% of these
lesions.
villous adenoma
(in book page 236)
Ulcerative colitis
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(ulceroinflammatory disease)
 affect the colon
 limite to the mucosa and submucosa
(except in the most severe cases)
 a systemic disorder
Morphologic features:
On gross, mucosa hyperemia, edema, and granularity.
(with easy bleeding)
In severely active cases, broad-based ulceration.
Histologic features: mucosal inflammation,
ulceration of the mucosa,
chronic mucosal damage.
(in book page 231-234)
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Morphology
Three natural narrow of esophagus
1. Favored Location:
EC
three natural narrow areas
20% of ～arise in upper third esophagus (5cm)
50% in the middle third esophagus (18cm)
30% in the lower third esophagus (1-2cm)
GC
Pylorus and antrum 50~60%;
Cardia 25%; remainder in body/fundus
Lesser curvature (about 40%) > greater curvature (12%)
So, favored location of ～: lesser curvature of the antropyloric region
CRC 50% arise in rectum, and 25% in ascending colon.
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2. Three gross pattern –take one of three forms
EC
●Exophytic polypoid or fungating form: mass protrude into the lumen
●Endophytic ulcerative form : ulcerative cancer mass extend deeply
● Diffuse infiltrative form: cancer mass impart thickening and rigidity
to the wall and lead to narrowing of the lumen.
2. Gross appearance: base on invasive depth-early and advanced ～
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GC (1) Early Gastric Carcinoma (E-GC) : confined to the mucosa and
submucosa, regardless of presence or absence of perigastric lymph node
metastases.
（basis on clinical data: 10％ of E-GC: lymph node metastases）
Two gross patterns: elevated form
Both have no obvious tumor mass
depressed form
in the mucosa (---)
Elevated form of E-GC
Depressed form of E-GC
2. Gross appearance
GC (2) Advanced Gastric Carcinoma (A-GC) : tumor mass
has extended below the submucosa into the muscular wall.
In some cases, perhaps has spread more widely.
A-GC have three gross forms:
(2.1) Exophytic polypoid or fungating mass (form)
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(2.2 ) Endophytic ulcerative form
(2.3 )Diffuse infiltrative mass.
This rigid and thickened stomach is called a
“leather bottle” stomach—革囊胃
(cancer mass imparts thickening and rigidity to
the wall, and lead to narrowing of the lumen)
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(2.2 ) Endophytic ulcerative mass
Gastric ulcerative carcinoma
larger, more surface，
significant elevated edges
gastric peptic ulcer
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Obvious differences between peptic ulcer and cancer ulcer: (list)
gastric peptic ulcer gastric cancer ulcer
the lesser curvature
the lesser and greater～
Location
Size / shape
1-2cm, round
Basis of depth
deeper
Margins
sharply
Surrounding mucosal folds radiate
Base of crater
clean
Cut section
an eroded artery
Histologic appearance
four zones
peptic ulcer
Cancer ulcer
＞２cm, irregular
more surface
elevation or beading
absent
necrotic gray
absent
invasion by malignancy
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2. Gross appearance
CRC
(1)Exophytic
Polypoid or
fungating
form
(2)Endophytic
ulcerative form
(3)Diffuse infiltrative (4) Mucinous mass
form
with a gel-colloid
appearance.
(mucinous
adenocarcinoma)
Microscopic appearance : carcinomas arise from
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superficial epithelium of mucosa or gland
EC
Squamous cell carcinoma constitute ＞90%
Well-
moderately-
poorly-differentiated
Adenocarcinomas: (<10%), arise from dysplastic
mucosa in Barrett esophagus.
(Mucin-producing adenocarcinoma)
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Microscopic appearance
GC Adenocarcinoma ＞90%
Squamous cell carcinoma (<10%): locate in cardia.

Histologic: gastric adenocarcinoma --- two major types:
intestinal- type
Malignant calls form neoplastic glands
Like glands of colonic--
diffuse-type
do not form glands
permeate the gastric wall
There are some differences between these two types (in book page 226-227)
 WHO Classification Method: well-, moderately-, poorly-differentiated.
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Microscopic appearance
GC
signet-ring cell carcinoma
Nucleous of tumor cell is
squeezed to cell margin,
like diamond in married-ring.
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Microscopic appearance
CRC
 Adenocarcinoma ＞90%
Special type: produce mucin
Signet-ring cell carcinoma:
Mucin present in tumor cells
Mucinous adenocarcinoam: Mucin is secreted
into gland lumina
 Squamous cell carcinoma (arising anal zone）
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CPC (clinico-pathological correlation)
In onset: insidious
In late stage － dysphagia and obstruction gradually
EC (食道癌)
Bleeding-hematemesis or melena
Other: weight loss, anorexia, fatigue,
weakness and pain (relate with swallowing)
E-GC: asymptomatic
A-GC: abdominal discomfort or weight loss
Locate in cardia: dysphagia
GC (胃癌)
Locate in the pyloric canal: obstructive symptoms
Other: melena, fatigue, weekness-Most cases: remain asymptomatic for years
To see doctor: Faeces with bright red blood, change in
bowel habit, and abdominal discomfort
CRC (大肠癌) Significant clinical features:
Faeces with bright red blood
Faeces like writing brush
Alternation of obstruction and diarrhea
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Bleeding: in these three tumors
As blood quickly congeals and turns brown in the acid
environment of the stomach lumen
Vomited blood: coffee grounds in patients with GC
bright red blood in EC
Faeces: melena (black- faeces) in patients with EC or GC
bright red blood in patients with CRC
Invasion and metastasis (浸润和转移)
Spread by direct extension into adjacent structures
For EC:
into

Upper third

Middle third
bronchus

Lower third
cardia贲门
larynx, trachea, thyroid (occurred)
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Invasion and metastasis
Spread by direct extension------
For GC: spread into greater omentum and pancreas
For CRC: spread into urinary bladder or uterus
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Invasion and Metastasis
2. Metastasis
 （for EC) Lymphatic
pathway: Spread to regional LN
late stage terminal LN - left supraclavicular L
（last region）胸导管－左锁骨上LN (Virchow

Hematogenous pathway: to distant sites
favored organs: Lung, liver and bone.
 Seeding within body cavities:
In females , tumor cells of GC seed to
both the ovaries,
krukenberg tumor (克氏瘤)
LN)
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Diagnosis
1. Endoscopy biopsy
2. Digital rectal examination : for rectal cancer.
Digital rectal
examination
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Prognosis: for all tumors
The most important prognostic indicator is
the tumor stage at the time of resection.
at Early stage: 5-y survival rate 90 ～ 95%， removed
at Late stage: 5-y survival rate 10 ～ 15% ，removed
So the only hope for cure of tumor is early detection and surgical remove.
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Related to gene alterations
Many studies indicate: genesis and development
of tumor relate to some genes.
EC - p53, p16
GC - c-met, K-sam, erb
CRC - APC
DNA repair gene
DCC（deleted in colon cancer)
p53
K-ras
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Colorectal carcinogenesis: two pathogenetically distinct
pathways for the development of colon cancer.
APC/β-catenin pathway
(adenoma-carcinoma sequence, or chromosome instability)
Mismatch repair pathway
(microsatellite instability)
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Colorectal carcinogenesis:
 both of these pathways involve the stepwise
accumulation of multiple gene’mutations.
 but the genes involved and the mechanisms are
different.
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APC/β-catenin pathway (p.239,Fig. 10-22)
Carcinoma
Normal colon
Adenomas
Mucosal at risk
APC at 5
APC/β-catenin
K-RAS at 12p12
P-53 at 17p13
LOH at 18q21
Telomerase
Many other genes
Mismatch repair pathway (p239, Fig.10-23)
Normal colon
Sessile serrated
adenoma
Alteration of second allele by LOH,
mutation, or promoter methylation
MLH1, MSH2
Microsatellite instability
Carcinoma
Mutations of
BAX,TCF-4, et al