• MUCOSA GÁSTRICA

• RESISTENTE AO PH ÁCIDO
DO ESTÔMAGO

H. PYLORI - ATIVAÇÃO DA RESPOSTA INFLAMATÓRIA - PROLIFERAÇÃO DE LINFÓCITOS B – FORMAÇÃO DE AGREGADOS LINFOIDES

H. PYLORI = GASTRITE
 CORPO + ANTRO + PILORO (PANGASTRITE)
 LINFOMA MALT
 ANTRO: s/ atrofia; inibição da produção de somatostatina
- SOMATOSTATINA = + ÁCIDO
 = ÚLCERA DUODENAL
 = LINFOMA MALT
 CORPO: c/ atrofia
ATROFIA = - ÁCIDO
 = ÚLCERA GÁSTRICA
 = LINFOMA MALT
 = METAPLASIA INTESTINAL = DISPLASIA = ADENOCARCINOMA

GASTRITE SUPERFICIAL (GASTRITE NÃO ATRÓFICA, SEM PERDA DE GLÂNDULAS)

→ GASTRITE ATRÓFICA MULTIFOCAL (COM PERDA DE GLÂNDULAS)
→ METAPLASIA INTESTINAL
→ DISPLASIA DE BAIXO GRAU
→ DISPLASIA DE ALTO GRAU
→ ADENOCARCINOMA (INVASIVO)
 Chronlc infection wi th H, pylorl Fia ella

Chronlc gastritls Antral gastrltls Corpus gastrltls

Norm.al ilCldity, no .atrophy 1 .acidlty, no illrophy 1 i!Cldity, .i.trophy

/''t/
No c1;n;c,1
symptom
MALT
lymphoma
vJ) ~ '

•
Duodenal utcer
•
Chronic atrophic gastritis

~
- vacuolaling toxin (vacA)

••
gastrlC mucosal lnjUry

Gastric ulcer Intestinal metaplasla

Dysplnla
Secntoryenzymes •••
- mucinase, protease, lipase
m.c:ton (cagAe.t.c) \
actin remodelling .

•
Adenocarclnoma
g~stric: m1,J1;osal injury IL-8 induction , host cell growth
and apoplosis inhíbition

.l!! High e.all

e
e
G)
Eo
cons1.1mptlon Smoking Antkucldants

e-
~.,
ou
·>-
e
w

,,.
i!?
·3 (O
. .,
cr-
u e

. .,
,,. :>
e a,

~
~

:i
Gene
polymorphl&m&

Westem

~~
.. o
AOH1C
EPHX1
ALDH-2
CMA
-E
.; IFNGR2 CYP19A 1
/L6 OR02
o SULT1A1 ER882 ~ - - - - - ~ CD44abanant transcrlpls
:i::
Cyclln E overa-xp,éeelon

··...... ····"'• •••••. •. . •........... •. . •• . . ·I CpG rnethylatlon (p1ô, MGMT, MLH1, RUNX3) ~ .............................................. .

Environmental factors
• Hlgh salt diet DNA
• Smoking damage
• Mutagens
· Etc.

~
~
Chromosome
breakage '---T
Chromosome
instability

Ac~rc .anlf G<1s1ric adcnocarci nQrna,

chronic gaslrilis non,Hodgldn's lymphoma
H. py/Ort

000000000

@
Dlsrupllon of
epilhelial barri@r lgA ~

lgGyY
•
- - IL·1~

NO
/ ........ TNF-a
GHIHB Malphage / IFN-y

ROS- Accumulation ol mutations Eplgenetlc gene B cell

(loss ol tumor suppressors expresslon changes IL-12 - IL-2
H. py!Ori
and actlvatlon ol oncogenes)
(arginase)
L T
1Gastric cancer 1- -----' . .:
•
.L
• lnllammaUon ,.h2cell
H. pylori
(VBCA)
 H. pylori and MALT lymphoma
a model of tumor progression

neutrophlls actlvatlons H. pylori chron ic gastritis

1. Persisting presence of H.pylori causes chronic
with release ot straln·speclllc "
inflammation genotoxlc !ree radicais stimulation "
2. lnflammation leads to infiltration of immune cells in
order to remove the microorganism
- B and T lymphocytes - production of antibodies
~'aB>-"i,,.. l
gene11c
~ Bcon1act-dependent@
B·cell stimulalion T
- Macrophages -production of APRIL B
, __ _
allerallons
B B anti~en solection T T T
5
- Neutophils - production of reactive oxygen species B auto1mmum1y

3. Reactive oxygen species cause damage to the DNA of B- H. pylorl-dependent mucosal

lymphocytes MALT lymphoma B-cell proliferation T-cell proliferation
4. May lead to overexpression of oncogenes or alteration l addilional genetic damages
of signalling pathways H. py/ori-independent ' - - - - - - + dlfluse larga B-cell lymphoma
MALT lymphoma

.------~ ~
~ Release of reactive
-------~--º-'Y_g_en_sp_ec_ie_s_ __ _ : - - - - - - - - - ~
Chemotaxis of
neutrophils
Continuous stimulation and Acquisition of
Acquisition of MALT
ar proliferation of B lymphocytes genetic anomalies

t
B cells

Recruitment and
activation of T cells

H. py/ori
eradication therapy
Decreased success rate

!. - - - - - - - - - - ,~ _ m_uec
_"k_h~_~_fs_"m_ ~ I ~ Gastric MALT lymphoma J~ t(11;18)(q21q21) J

1(1;14)(p22;q32)
t(3;14)(p13;q32)
Diffuse large Unknown ~ . 1 1(14;18)(q32;q21) - - - - ~
B-cell lymphoma - mechanism (FOXPl?) Gastnc MALT lymphoma Aneuploidy
other genetic
aberrations

normal
B-ce ll normal
B-cell
H.py/ort
autolmmune
Chlamydla
others
Eplgenetic abnormalities Genetic abnormalltie s
Aberroa t hvoer-merhvfatioa
KIP2, P16, DAPK, MGMT T-cell
t(1 1;18)(q21;q21}
MINT31 , HCAD, MINT2

MALT Lym phoma Low mallgnancy MALT Lymphoma

MINTl 1(1 ;14)(p22;q32)

•
NOTA• FAS mutatlon
de novo
Mucosa-associated lymphoid tissue includes the high grade MALT Lymphoma
fol lowing structures:
- Lymphatic pharyngeal ring with the
pharyngeal, lingua l, and palatine tonsils; P53 mutatlon & LOH
- Gut-associated lymphoid tissue (the fol l icles P16 deletlon
of the duodenum, appendix, colon);
- Bronchi-associated lymphoid tissue
(in the peribronchia l fasc ial sheath);
- Exocrine glands (sal ivary glands and pancreas);
- Mammary glands.
 • The particular end result of H. pylori infection (gastritis,
Pathogenesis PUD, gastric MALT lymphoma, gastric cancer) is
determined by a complex interplay between bacterial
• H pylori grows optimally ata pH of 6.0-7 .0 and
and host factors.
would be killed or not grow at the pH within the
gastric lumen.
• Gastric mucus is relatively impermeable to acid and
has a strong buffering capacity.
• On the lumen side of the mucus, the pH is low (1.0-
[Z]
Bacterfal f actora Hoat factora
Stl'Uciure Ouratlon
2.0) while on t he epithelial side the pH is about 7.4. Adhesins Location
Porins lnttanvnatory response
• H pylori is found deep in the mucous layer near the Enzymes Genetics??
(urease, vac A. cag A. etc.)
epithelial surface where physiologic pH is present.
Clwonic gastritis
Peptic ulcer diseasa
Gastric MALT lymphoma
Gastric cancer

Bacterial factors • H. pylori makes proteases and phospholipases that

• H. pylori is able to facil itate gastric residence, induce
mucosal injury, and avoid host defense.
• Different strains of H. pylori produce different
virulence factors .
break down the glycoprotein lipid complex of the
mucous gel, thus reducing the efficacy of this first
line of mucosal defense.
H. PYLORI CROSSING MUCUS LAYER OF STOMACH

• A specific region of the bacterial genome, the

pathogenicity island (cag-PAI), encodes the viru lence

• Vac A also contributes to pathogenicity, although it is

not encoded with in the oathogenicitv island .
• These virulence factors, in conjunction with additional
bacterial constituents, can cause mucosal damage, in
part through their abi lity to target the host immune
cells .
c;asuk:
H.pYIO<i mudn
gel

Host factors
• Elevated concentrations of multiple cytokines are
• The inflammatory response to H. pylori includes found in the gastric epithelium of H. py/ori-infected
recruitment of neutrophils, lymphocytes (T and B), individuais, including interleukin {IL) 1/, IL-2, IL-6, IL-8,
tumor necrosis factor (TNFa), and interferon {IFN-y).
macrophages, and plasma cel ls.
• H. pylori infection also leads to both a mucosal anda
• The pathogen leads to local injury by bind ing to class systemic humoral response, which does not lead to
li major histocompatabi lity complex (MHC) eradication of the bacteria but further compounds
epithelial cell injury.
molecules expressed on gastric epithelial cells,
• Additional mechanisms by which H. py/ori may cause
leading to cell death (apoptosis) . epithelial cell injury include
• Moreover, bacterial strains that encode cag-PAI can (1) activated neutrophil-mediated production of
introduce Cag A into the host cells, leading to further reactive oxygen or nitrogen species and enhanced
epithelial cell turnover and
cell injury and activation of cellular pathways
(2) apoptosis related to interaction with T cells (T
involved in cytokine production.
hei per 1, or T.,1, cells) and IFN-y.
 H. PYLORI - LINFOMA DE MALT GÁSTRICO

Figure 3: MALT Lymphoma of Stomach: Compared to chronic gastritis, the lymphoid infiltrate in MALT lymphoma
extends deeper into the lamina propria (a, H and E, ×20). Immunohistochemistry for CD20 shows many B-cells (b,
×10), and contains lymphoepithelial lesions in which neoplastic B-cells infiltrate and eventually overrun epithelial
structures (c, CD20, ×40)
 Morphology of MALT and gastric MALT lymphoma from the gastrointestinal tract
The Peyer's patches are characterised histologically by the presence of a germinal centre (GC) surrounded by a
follicular mantle (FM) and a marginal-zone (MGZ). Intraepithelial marginal-zone B cells (IEBC) are observed within the
epithelium covering the Peyer's patch, forming the lymphoepithelium characteristic of MALT. The morphology of
gastric MALT lymphoma. The germinal centre (GC), where B cells proliferate and mature following antigen stimulation,
is surrounded by a follicular mantle (FM), which comprises naive B cells. The reactive B-cell follicle is surrounded by
neoplastic marginal-zone (MGZ) B cells that infiltrate the neighbouring epithelium forming characteristic
lymphoepithelial lesions (LEL).
Source publication
 Acute gastritis: Histology

Lack of chro nic inflammatory ce ll s

ll
Helícobacter pylorí
gastritis :
A, Spira~shaped H. pylori
are highl ighted in this
Warthin-Starry silver stain.
Organisms are abundant
wi thin su rface mucus.
B, lntraepithelial and lamina
propria neutrophils are
prominent
e, Lymphoid aggregates
with germinal centers and
abundant subepithelial
plasma cells within the
superficial lamina propria NORMAL PYLORlC
are characteristic of H. pylori MUCOSA Gi\STRITIS
gastritis Web /mage 20.10: A,Chronicalrophlc gastri~s(rlghl)contrasted wi!h normalpylorlc mucosa (left). There Ismarked
gastric atrophy withdisappearance of gastric glands and appearance of goblet cells(intestinal metaplasia). B,
Pholomicrograph showingchronicatrophicgastriliswith intestinal molaplasia.

Chronic gastritis showing partial replacement of the Chronic Gastritis Lymphocytes, +/- PMN
gastric mucosal epithelium by intestinal metaplasia lymphold folllcles
(upper left) and with inflammatíon of the lamina propría - METAPLASIA,
involving (right) lymphocytes and plasma cells. Intestinal
~il'lflt•MIUlf}'
,- CUtll ;tflftllõc.f•WIC'IUl'
- ATROPHY, mucosa!
" thlnnlng"
DYS -PLASIA

Chro nic Gastritis

Morphology
Chronic lnf lammation with or without
activity
Regenerative epithelial change
Complications of Chronic Gastritis
Pe ptic ulcer disease
Mucosa! atrophy
Intestinal met aplasia, dysplasía, gastric
carcinoma
H.Pylori associated MALT lymphoma
 Morphology of Chronic Gastritis Intestinal metaplasia
Regenemtive Change.
Plefers to the repl.:)cernent of iastric epitheliurn with colurnnar
ProliferatÍ\"t.' rcsponsc to cpithclial injury
and ioblet cells of intestinal variety~ Paneth cells and
l\cck rcgion of gastric glands mitotic figures incrcascd endocrine cells rnay also be present.
l ·:nlargcd cpithclial ccll \\'ith hypcrchrnmatic nuclci and
Gastric intestinal type carcinomas appear to arise frorn
highcr 1\/C ratio & promincnt nuclcoli
dysplasia of this rnetaplastic epitheliurn.
Rcgcncrative changcs if scvcrc with activc inflammation
resemble dysplasia

Metaplasía.
/ lntrnl, body, aml fundic mucosa may bccomc partially
replaced by metaplastic columnar absorptive cells anel
goblct cells of intestinal morpholo.l,'Y (intestinal
metaplasia). Occasionally, villus-likc projections or
fratures of colonic epithelium may be present. H.pylori
abscnt from arcas of intestinal metaplasia

Stratified squamous
epithelium

paneth ce lls and variety of endocrine cel ls

Photomicrogr, phs of g, hfo int e. lin, l m~inpl ia. (a) ompl~le ·type wifü well-
defi11ed gobl t cell~ altemating witll eosinophihc e11.t roc es displaying well·
develop d brash bo i-der (ln t) and Pa11etl1 e lls (arrow). ) Jnoomplete type
showi11,g omltlpleintracytopla micmnein drople o varying lze a11d hapes,
and abs.ente of a hrush border. (Hemaloxylln and eosín; original m~alfic:ill.cn,
NORMAL NORMAL

NORMAL
 Norma!
Normal gastric
mucosa

Acute gastritis

Gastrí1ís
1
Chronic gastritis

Atrophic gastritis Atrophic

1
gastritis

Intestinal metaplasia

Dysplasia
1
1
Oysplasia

Adenocarcinoma
Cancer

Norma I gastric

, .......................... - ............ t
'
: 1'" free radicais
.
: '
j .. .

TERT activatiot' !i
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ., 1-·---·----···--·········1 ---------------------- -- --.
APC, pS3 anel m~tatlon j LOH TP53, APC and BCt2
: 1' expres"Sion of TNFo:, : -.t,.. RARtl expresslon : ! MLHl me1hylalion l ,1, pi7 and TGF6RI e~pre,,ion,
:
i'
ll-G and IL-10
DNA Hvpermethylation
.
:
:
t
?5.3 O\'ere,xpre$$iOn
aberrant C044 transcript
'L--- - - - - - - - - - - - - - - - - - - - - - _ ,.. _, .
•, MSI
1t_ ___ ___ _ __ __ _____ ________ :
1
EGFR, ERB82 ampllflcations
VEGFA ampllficatlon
PIK3CA, KRAS/NRAS mutations
:
'
MSI
.
:
I. . - - - - - - - - - - - - - - - - - - - - - ·

Normal gastric
r.
:
-~~:t:::·;;;~~;a·t;;; •• '
TERT act iv.1t lon : E-c.ad he.rin loss /mutation
t. _ - -- -- ---- - ---- --- - ____ ,

l7q2HOH
TP53 LOH/mu tation

FGFR2F, MET, MDM2 ampllficatlon,

RHOA mut atíons
......... --·-------·--···--·---- ...... 1
Diseases of the Stomach GASTROINTESTINAL SYSTEM
TABLE 4-2 HISTOLOGIC CLASSIFICATION OF GASTRITIS

Type of Gastritis Histologic Features Course

Common acute Mu casal edema Usually transient

gastritis Neutrophilic infiltration with or
\Nithout erosions
Petechiaewith orwithout mild
lymphoplasmacyt ic infiltration
Epithelial regeneration in neck
Superficial region of glands
erosions
Eosinophilic gastritis Eosinophi lic i nfiltrates of ai 1 Incidental or recurrent (may be
layers, frequently with re late d to allergies or ingestion
mu scular hypertrophy of chemical irritants )

Chronic type B gastriti s Superficial lymphoplasmacellular Chronic persiste nt or recurrent

{more common) infiltrate May predispose to carcinoma
Neutrophils if erosive, with or or lymphoma
Acute gastritis without lymph follicles
(gastroscopic view) Colonization by He!icobacter
pylori
Elongation of glandular necks
with epithelial regeneration
Intestinal metaplas ia in late phase

Chronic type A gastritis Patchy lymphocytic infiltrate with Chronicaggress ive

invasion of crypt epithelia and Decreased vitamin B, 2 resorption
epithelial degeneration may predispose to cancer *
Loss of acidophilic cells
Intestinal metaplasia

*Decreased vitam in 8 12 resorption is followed by various B, 2 deficiency diseases, such as pernicious anemia,
sp ina l cord demyelination1 and others .

Hypertrophic
gastritis (e.g., in alcoholism)

Erosive (hemorrhagic)
gastritis in section of
lower stomach

Gastroscopic view

Pylorus

FIGURE 4-6 GASTRITIS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Gastritis ís the most common cause of upper abdomínal paín ín
adults. Gastroscopy dífferentiates the gross features of acute
gastrítís, erosive gastrítís, hypertrophíc gastrítís, and chroni c
(atrophic) gastritis. Biopsy and pathologic investigation offer a
more exact classifícation of pathogenesís and prognosís (Tab le
4 -2). Acute gastritís ís usually caused by chemícal írrítatíon by
alcohol, cígarette smoke, or drugs (e.g., aspírín, nonsteroidal
antíínflammatory drugs, chemotherapeutics), uremía, or suícídal
ingestion of acids or alkali. Severe stress can ca use acute gastritis
with erosíon and ulceration ("stress ulcer"). Systemíc ínfectíons,
shock involving the stomach, loss of pyloric function (e.g., after
surgery) or duodenobílíary reflux can ínítiate acute gastrítís.
lnfection with Helicobacter pylori accounts for 50% to 80% of
cases of chronic type B gastrítis. Chronic type A gastrítis, an
autoí mmune gastrítís, may occur alone or accompany other
autoimmune dísorders (thyroiditis, ínsulin-dependent díabetes
mellítus, Addíson dísease).

105
GASTROINTESTINAL SYSTEM Diseases of the Stomach

Atrophic
gastritis
1

)
----?......--+--- Section of lower
stomach

Pylorus

Thinning of
mucosa with
prominent vessels

Gastroscopic view

Atrophic gastritis with intestinal metaplasia. Atrophic gastritis with intestinal metaplasia.
The mucosa is thinned and much of the surface This gland shows dysplastic changes with epithelial
mucosal epithelium and glandular epithelium is cell atypia manifested by nuclear enlargement and
replaced by intestinal epithelium with mucus- increased chromatin (high-power view).
containing goblet cells (arrows). The lamina
propria contains abundant inflammatory cells
(low-power view).

FIGURE 4-7 ATROPHIC GASTRITIS - - - - - - - - - - - - - - - - - - - - - - - - -

The pathologic term atrophic gastritis is reserved for chronic
gastritis with intestinal metaplasia (i.e., specífic crypts of the
gastric corpus are replaced by intestinal glands with goblet cells).
Glandular necks are markedly elongated with extended epithelial
regeneration involving surface epithelia and increasing amounts
of dysplastic glands and epithelial atypia. Patients with atrophic
gastritis have the highest risk of developing gastric cancer. Table
4 -2 summarizes the histologic features and the courses of various
types of gastri tis.

106
Diseases of the Stomach
FIGURE 4-8 PEPTIC ULCERS - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Peptic ulcers (PUs) of the stomach or duodenum represent
approximately 98% of ulcerations in this region. PUs are usually
chronic, whereas th e less common "stress ulcers," which may
accompany extensive burns, severe trauma, or other situations of
excessive stress or the administration of certain drugs (corticoste-
roids), are acute. The pathogenesis of PU includes excessive
action of gastric acid and pepsin, reduced mucosal defense
mechanisms (e.g., reduced mucus production, reduced epithel ial
GASTROINTESTINAL SYSTEM
Sarne ulcer viewed
regeneration such as in tobacco smoki ng), and, frequently,
infection with H pylori. PUs require treatment because of the
possibility of complications, including acute or chron ic hemor-
rhage and anemia, perforation, chronic scarri ng and stenosis
(e.g., in pyloric or postpyloric ulcers), penetration into adjacent
organs (e.g., into the pancreas with subsequent pancreatitis), and
development of carcinoma within the regenerating mucosa
adjacent to the ulcer.
107
GASTROINTESTINAL SYSTEM Diseases of the Stomach

Wall of duodenum

Duodenal ulcer

Duodenitis with
erosions

Deformities of duodenal bulb with niche due to ulcer (arrows)

FIGURE 4-9 DUODENAL ULCERS - - - - - - - - - - - - - - - - - - - - - - - - - -

Duodenal ulcers are usually located in the anterior or posterior pathogenesis and complications of duodenal ulcers resemble
wall of the bulbus and occur secondary to hyperacidification. The those of stomach ulcers, although malignant transformation to
mucosa in this areais especially sensitive to acid juices. The cancer is rare.

108
Diseases of the Esophagus GASTROINTESTINAL SYSTEM

Esophagoscop ic
view

Esophagus

carcinoma

Fungating
carcinoma

FIGURE 4-3 ESOPHAGEAL CANCER: SQUAMOUS CELL C A R C I N O M A - - - - - - - - - - - - - -

Malignant neoplasms of the esophagus account for up to 2% of
cancer deaths in the United States annually. Certain ill-defined
genetic predispositions, exposure to food carcinogens (e.g.,
nitrosamines), tobacco smoke, chronic alcoholism, and chronic
esophagitis (especially with BE) seem to be important pathoge-
netic factors. Loss of p53 tumor suppressor gene function is one
of the most frequently observed molecular changes in esophageal
cancer. Squamous cell carcinoma usually impresses as a
plaqueli ke or fungati ng white lesion in the upper or medial part
of the esophagus. The tumor infiltrates the esophageal wall
deeply, penetrates into the mediastinum, and spreads via
lymphatic channels. lnvasion of the bronchial tree may occur
with fistulation. Severe dysphagia and anorexia cause pro-
nounced cac hexia. The 5-year survival rate is 10% for patients
with squamous cell carcinoma.

101
Diseases of the Stomach GASTROINTESTINAL SYSTEM

Diffuse scirrhous
infiltration of
gastric wall
(linitis plastica)

Malignant infiltration

Linitis plastica Scirrhous carcinoma

(Van G ieson, X 250) (hemalum-eos in, X25 0)

FIGURE 4-10 CARCINOMAS OF THE STOMACH

Carcínomas of the stomach are among the most common tumors
in the Western world and Japan. Approximately 50% develop in
the antrum or pyloric regi on, approximately 25% develop in the
corpus, and 25% deve lop in the fundus. Most tumors are located
in the lesser cu rvature. Their gross features vary from mucosal
flattening and thickening with erosions to diffuse thickening of
the gastric wall (linitis plastica), to large ulcers or polypoid-
fungating masses. Stomach carcínomas are classified as type 1:
protruding nodular or polypoid lesion; type li: slightly elevated o r
depressed flat lesion; and type Ili: excavated or ul cerated lesion.
There are 2 main histologic types of classic carcinoma of the
stomach: the intestinal type with tubular glands, which si mui ates
atypical intestinal mucosa, and the diffuse type with extensive
mucus production by signet ring cells (signet ring cell carcinoma
and linitis plastica including also less mature cells). Polypoid
adenocarcinomas are found in the ca rdia and in rare preexistent
adenomas.

109
GASTROINTESTINAL SYSTEM Diseases of the Stomach

Polygram.
Demonstrati ng
rigidity of segment
oflesser curvature

Somewhat
more advanced
carcinoma

FIGURE 4-11 EARLY GASTRIC CANCER - - - - - - - - - - - - - - - - - - - - - - - -

Early gastric cancer is a pathologic term for a tumor confined to
mucosa or submucosa. lt is generally asymptomatic and is
detected only by chance. Patients with this tumor have a 10-year
survival rate of 95% after surgi cal intervention; patients with
other stomach tumors have a combined survival rate of only
20%. Advanced gastric cancer also may be clinically occult
exceptfor undefined abdominal discomfort and weight loss.
Large tumors in the prepyloric area may cause obstruction. Acute
massive bleeding, even in ulcerated tumors, is uncommon,
whereas chronic bleeding with significant anemia is frequently
observed.

110
Diseases of the Stomach GASTROINTESTINAL SYSTEM

Extensive carcinoma
of stomach. With
metastases to lymph
nodes, liver, omentum,
tail of pancreas, and
hilus of spleen;
biliary obstruction

Spleen

TABLE 4-3 PATHOGENESIS OF CARCINOMA OF THE STOMACH

Factors Prevalence and Examples

Nutritional factors Apparently accou nt for geographic variations in cancer incidence: large amounts of smoked fish, pickled
vegetables, highly salted foods; diets low in fruits and vegetables (i.e., in protective antioxidants)
ldentified carcinogens: nitrosamines, benzpyrene

lnfections Chronic Helicobacter pylori infection as cofactor (see above)

Genetic factors Approximately half of cancer patients possess blood grou p A

No clearcut genetic traits identified
Changes in tumor suppressor gene activity (e.g., p53), germline mutations, and genetic mismatch repair
similar to cancer of the colon (see there)

Other factors Low socioeconomic status (probably related to nutritional factors and infection)

flGU RE 4-12 SPREAD OF GASTRIC CARCINOMAS - - - - - - - - - - - - - - - - - - - - -

AII gastric carcinomas spread by direct extension to nearby
organs or metastasize via lymphatic channels and the blood-
stream. Even i n early cancer, there is a 5% risk of regional
lymphatic metastases at the time of initial tumor diagnosis. The
most common sites of metastasis are lymph nodes at the lesser or
greater curvature of the stomach, in the subpyloric region, and in
the porta hepatis. More distant metastases i nvolve the left
supraclavicular lymph nodes (Virchow node), the I ungs, the bone
marrow, and the ovaries (Krukenberg tumor). The etiology and
pathogenesis of gastric cancer are reviewed i n Table 4-3 .

111