CANCER OF THE
STOMACH
Epidemiology
2nd commonest cause of Ca related mortality worldwide
700,000 deaths per yr worldwide
In 2002 (USA) – 22K new cases, 12k died
Predilection for elderly pts (50–70s)
Males > females
Marked geographic and ethnic variations in incidence
Blacks x 50% increased risk cf whites
Inversely related to social class
In Uganda – 2nd commonest GI ca (1st Ca oesophagus )
Ca has decreased in the west – bacterial eradication,
improved sanitation
Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002: Cancer incidence,mortality
and prevalence worldwide, Version 2.0. IARC CancerBase No. 5. Lyon:
Risk factors- host, bacterium, environment
Diet
- High salt/ smoked/ poorly preserved
foods : salt suppresses parietal cells, and
salty diets cause gastric atrophy
- low fresh friut/ vegs: Presence of vits C, E,
carotenoids and flavanoids- antioxidant,
inhibit nitrosamine formation, dilute or bind
carcinogens
- Foods rich in nitrates, nitrites, secondary
amines – combine to form nitroso amines=
carinigenic
- Green tea – anti carcinogenic
-
Infectious agents
1. EBV – in all types, but more linked to
undifferentiated form called
lymphoepithelioma – like carcinoma.
(histology like nasopharyngeal ca)
2. H. pylori (class 1 carcinogen)
– inflammation,
- Genotypic variants: Vac A toxin, CagPI,
- (type 1 strain). Also baba2 gene more
virulent
Low acid predisposes to cancer via
various mechs:
- Impaired Vit c absorption
- Overgrowth of salivary and intestinal
bacteria within the stomach.
Proximal gastric ca (at the gastro-
eosophageal jxn) is associated with
normal acid output.
Distribution of gastritis determines acid
secretion and clinical outcome of infection.
Gastric atrophic pangastritis – ass with h.p
is the most risk factor for distal ca.
About 20% cancers are multicentric
Correa’s model of gastric
carcinogenesis
Genetic predisposition / make up of the host
- 1st degree with ca = x2-3 risk
- Same exposure?
Hereditary non polyposis colon cancer syndrome (lynchh
syndrome 11)
Hereditary diffuse Ca syndrome
Polymorphism in pro-inflammatory cytokines
Familial adenomatous polyposis
Germline mutations of E- cadherin – true herediatary ca –
implicated in hereditary diffuse ca; therefore screen,
prophylactic gastrectomy
Gastric adenomatous polyps
Peutz Jeghers syndrome
Pernicious anaemia
Partial gastrectomy
- long term risk of ca is increased. Low in first 15-20yrs
- Billroth II > I
- Decreased gastric acid = increased bacteria esp
anerobes which convert dietary nitrates to nitrites
- Bile reflux promotes gastric epithelial proliferation =
metaplasia
Menetriere’s disease (giant hypertrophic
gastritis)
Smoking
Chronic atrophic gastritis
Intestinal metaplasia
Exogenous chemicals
Intra-gastric synthesis of
carcinogens
Blood group A
Classification
Location
DISTAL PROXIMAL (CARDIA)
Areas with high More in Caucasians and
incidence of ca low incidence of ca
stomach
Related to H.Pylori Consequence of chronic
infection GERD and Barrett’s
esophagus
Macroscopic appearance –
(Borrmann)
Type 1
Polypoid lesions without necrosis or
ulceration
Type 2
Fungating cancers, may have ulceration
Type 3
Ulcerated lesions infiltrating the stomach wall
Type 4
Diffusely infiltrating tumours or linitis plastica
LP- aggressive infiltrating tumour ass with a
marked desmoplastic reaction = rigid
leather bottle stomach. Poor prognosis
WHO histology typing
Early gastric cancer
Cancer confined to the mucosa / sub-
mucosa- diagnosed before it has
penetrated the full thickness of the
stomach wall or metastasized
< 5% in the west
With aggressive mgt- > 90% survival
The African enigma:
Low rates of Ca despite high H.pylori
prevalence ?
- Concurrent helminthic infection converts the
T helper cell (Th 1 response) which normally
promotes cell mediated immune responses
and tissue injury to a less damaging Th2
response
- So the progression of Helicobacter
associated gastric atrophy, a premalignant
lesion is changed.
Symptoms
Asymptomatic
Pain, epigastric (80%) - like PUD, advanced –
back below scapula.
Anorexia, weight loss
Vomiting: persistent – antral tumours with GOO
Dysphagia: Cardia tumours
Early satiety – infiltrative ca= loss of
distensibility
GIT bleeding: Hematemesis, melena
Signs
No signs
Cachexia / weight loss / Anaemia
Epigastric mass
Left supra-clavicular node (Troisier’s sign) – rare
Irish node – axilla
Symps and signs of metastases- liver, ovary
Paraneoplastic symps
- Acanthosis nigricans: Dark skin in axilla and neck
- Membranous GN
- Microangioapathic hemolytic anemia
- Arterial and venous thrombi ( Trousseau syndrome)
- Seborrhoiec dermatitis (Leser Trelat sign)
- Dermatomyositis
Investigations
Endoscopy and biopsy
- Diff to tell benign and malignant ulcers- so take several biopsies (6-10)
from all parts of the ulcer
- Brush cytology adds sensitivity
Ba meal- double contrast
- For anatomy and degree of obstruction
- Diagnosis of linitis plastica- can be missed at endoscopy
- If dysphagia- do Ba swallow also
CT, Laparascopy and endoscopic u/s- done for staging esp pre-
surgery
U/S
Light induced fluorescence endoscopy (LIFE)
MRI
PET – preferential emission by tumour cells
Biochemical markers
- CEA
- Pepsinogen – low levels ass with
gastric atrophy
- Serum gastrin levels > 200ng/L- low
sensitivity but is specific
- Serum protein profiling
Choice of mgt
General health and nutrition
Staging
Facility capabilities
Endoscopic therapy
ENDOSCOPY
MUCOSAL
RESECTION /
ENDOSCOPIC
STRIP BIOPSY (T1
STENTING -
tumor)
OTHERS:
- ENDOSCOPIC SUBMUCOSAL DISSECTION
-LASER ABLATION
-ARGON PLASMA COAGULATION
SURGERY
Removal of primary tumour
- Total Vs Distal / proximal gastrectomy
/ oesophago-gastrectomy
Lymph node dissection
Laparascopic surgery for gastric
resection
Chemotherapy
- Preop (neoadjuvant), intra- or post-op
- Agents: 5-fluor-uracil, cisplatin, hydroxyurea,
adriamycin
- Combination / single drugs- varying effectiveness
- Systemic or intra-peritoneal admin
Radiotherapy
- Most are unresponsive
Chemo-irradiation
Full Package
- Pain mgt- including celiac plexus blocks
Spread
Local extension
- Gastro-colic fistula = vomiting faecolith
material, pass ingested food in stool
Lymphatic
- Early
- Virchow’s node
Hematogenous: Liver, bone, brain
Peritoneal
- Sr. Mary Joseph node
- Krukenburg tumour
- Blumer shelf (tumour mass in cul de sac)
Prognosis
About 50% are incurable at diagnosis
Regional nodes – 5yr survival after
gastrectomy is 10%
Only perigastric nodes – 30%
Confined to stomach – 70%
Only 10% hepatic mets survive for 1 yr
Proximal ca has worse prognosis than
distal ca
Issues
Chemo-prevention: interventions with
pharmaceuticals, vits, minerals or other natural /
synthetic chemicals at any stage of carcinogenesis
to reduce ca incidence
- H.pylori eradication- ? No role in preventing
progression but prevents metaplasia/ pre- ca
lesions
- Supplementary anti-oxidants (ß carotene, ascorbic
acid) – regression of metaplasia and atrpohy
Screening – target high risk groups
? Pts who are H.pylori positive and have cancer-
Role of eradication
Other gastric tumours
Gastric lymphoma
- B cell non Hodgkin
- Low grade mucosa associated lymphoid tissue lymphoma
(MALT) - low grade gastric B cell lymphomas arising from
mucosa. Driven by T cell stimulation which is driven by H. pylori
antigen stimulation. Can occasionally improve on antibiotics and
PPI
- Large cell diffuse lymphoma
Mesenchymal tumours of the stomach
Endocrine tumours of the stomach
- Gastric carcinoid tumours
Gastric polyps
- Hyperplastic polyps
- Adenomas
- Leimyomas
Fundic gland polyps- Commonest non neoplastic polyp in the
stomach
Asymptomatic and no risk of malignant change
Usually incidental findings on upper GI endoscopy
References
1. Textbook of Gastroenterology – 5th
edition. Edited by Tadataka Yamada
2. Principles of Clinical Gastroenterology
3. Uemura, Okamoto et al: H. pylori
infection and the development of
gastric cancer. N Eng J Med.
2001;345:784-9. PMID: 11556297
