1.

Stomach and
2. esophageal cancer

Stomach cancer-Anatomy
Parts of the stomach:
-cardia (cardiac portion)
-fundus
-body
-pyloric antrum
-pyloric canal

1 . C A R D IA C P O R T IO N

2. FUN D U S

3. B O DY

5 . P Y L O R IC C A N A L
4 . (P Y L O R IC ) A N T R U M
P Y L O R IC P O R T IO N

-cancer on the lesser curvature is more frequent than on the greater

- cancer in the body or antrum more frequent but cancer in the cardiac
region is increasing rapidly the Western world (still, everywhere, body and
antrum are more frequent)

Epidemiology
Adenocarcinoma of the stomach was
the leading cause of cancer-death
worldwide through most of the 20th
century (1901-2000)
-now ranks second to lung cancer
Its incidence had an ever more
marked decline in North-America and
Western-Europe

Epidemiology-US males

Epidemiology-US females

In Romania:
-second cause of cancerdeath in males
-fifth in females

Etiology (risk factors)

I. Genetic factors
Hereditary diffuse gastric cancer

(E-cadherin mutations,

autosomal dominant disease)

Blood type A
Pernicious anemia
Familial adenomatous polyposis (FAP),
Hereditary nonpolyposis colon cancer
Li-Fraumeni syndrome
BRCA1/2 mutations
Family history (other, yet unidentified genetic factors)

II. Precursor lesions

Adenomatous gastric polyps
Chronic atrophic gastritis
Dysplasia
Intestinal metaplasia
Menetrier's disease

Etiology (risk factors)

III. Environmental factors
Helicobacter pylori infection
Nutritional
High salt consumption
High nitrate consumption
Low dietary vitamin A and C
Poor food preparation (smoked, salt cured)
Lack of refrigeration (mycotoxins)
Poor drinking water (well water: nitrates)
Occupational
Rubber workers
Coal workers
Cigarette smoking
Epstein-Barr virus
Radiation exposure
Prior gastric surgery for benign gastric ulcer disease [scaring and
regurgitation of the (irritant) bile]

Histological subtypes-Laurens
classification

Adenocarcinoma
a) Intestinal type
-microscopically: gland formation
-related with H. pylori
-related to precancerous conditions: chronic gastritis, atrophy,
intestinal metaplasia
-increasing incidence with age
-men>women
b) Diffuse type
-less well differentiated, characterized by sheets of cells without
gland formation, with the occasional presence of signet ring cells
and mucin
-related with H. pylori, but genetic factors more important
-not related to the above precancerous conditions
-mostly younger patients
-women>men
-worse prognosis

Intestinal type

Chronic gastritis with intestinal metaplasia:

The mucinous gastric epithelium
(arrowhead) is replaced by intestinal type of
epithelium (arrow).

Gastric cancer-intestinal type

Diffuse type

Macroscopic subtypes-Bormanns
classification

Bormann type 1: polypoid or

protuberant carcinoma (usually a welldifferentiated adenocarcinoma)
Bormann type 2: expansive ulcerating
carcinoma (deep ulcer with elevated
margins)
Bormann type 3: infiltrative ulcerating
carcinoma
Bormann type 4: diffusely infiltrating
carcinoma= linitis plastica.
Bormann type 5-unclassifiables
The macroscopic appearance is of
prognostic value: higher the Borrmann
type number, worse the prognosis

Extension of stomach cancerdirect extension

Greater omentum
Lesser omentum
=hepatogastric ligament
Colon
Pancreas
Duodenum
Cardiac tumors (stomach
extraperitoneal): diaphragm

Extension of stomach cancerperitoneal extension

possible after a lesion extends beyond
the gastric wall to a free peritoneal
(serosal) surface
Krukenberg tumor (mucin-secreting
signet-ring cell metastasis on the
ovary from gastrointestinal or breast
cancers)
Blumers shelf (i.e. shelf-like tumor of
the anterior rectal wall)

Extension of stomach cancerlymph vessels->lymph nodes

Regional lymph nodes: mainly along the arteries:
-lesser and greater curvature
-celiac
-splenic hilum
-hepatic hilum
-pancreatico-duodenal
-some paraaortic (in the Japanese staging)
Lymph nodes where spread is considered
metastasis:
-paraaortic
-mediastinal
-left supraclavicular (Virchow's)
-left axillary (Irish)
-umbilical (Sister Mary Joseph's)

Extension of stomach cancerhematogenic metastases

Liver
Lung
Bone
Brain

Clinical features
Late (cancer limited to the stomach in
about 15% of patients)
Nonspecific signs and symptoms:
-Weight loss
-Anorexia (sometimes selective anorexia
to meat)
-Abdominal pain (can be similar to that in
ulcer)
-Anemia secondary to chronic blood loss

Clinical features
Proximal cancer:
-dysphagia
Distal cancer:
- gastric outlet obstruction: nausea, vomiting
Linitis plastica:
-early satiety (decreased gastric capacity)
Other signs and symptoms:
-hematemesis (rarely)
-left supraclavicular adenopathy, left axillary
adenopathy
-paraneoplastic syndromes: venous thrombosis etc.

Diagnosis
Barium Meal
-Better tolerated
-Sensibility: only 50%
Upper GI endoscopy-gold
standard
-Sensitive and specific
-can perform biopsy
-more expensive

Diagnosis
CT or better, MRI of the abdomen
(lymph nodes and peritoneal/hepatic
metastases)
EUS (endoscopic ultrasonography)
can help decide resectability
Pulmonary radiography
High resource setting: PET/CT

Staging
Gastric cancer is a surgically staged disease

-TNM staging
Tis-in situ tumor
T1-invading the lamina propria or
the submucosa
T2-muscularis propria/subserosa
T3-serosa
T4-adiacent organ involvement
N0: no positive lymph nodes
N1: 1-6 lymph nodes positive
N2: 7-15
N3: more than 15

Japanese TNM staging

Treatment
RESECTABLE TUMORS
Tis and T1 tumors limited to de mucosa (T1a) can be
managed by endoscopic mucosal resection
T1b-T3 N+/- : gastric resection with at least 4 cm margin
(- Wedge resection
-Segmental resection
-Proximal gastrectomy
-Pylorus preserving gastrectomy
-Distal gastrectomy
-Total gastrectomy)

T4 tumors require en bloc resection of invaded structures

Gastric resection should include D1+D2 lymph node
resection
(D1=perigastric lymph nodes; D2=those along the named
arteries of celiac axis. At least 15 lymph nodes have to be
excised.)

HE staining for lymph nodes is not enough;

misses 50% of lymph node meta=>additional
cytocheratin staining is used

Treatment
RESECTABLE TUMORS
After surgery in T3-T4 N0-N1 patients:
In Europe and America:
-usually there is no correct D2 resection
STANDARD: adjuvant chemo-radiotherapy
In Japan:
-usually there is a correct D2 resection
STANDARD: adjuvant oral chemotherapy plus
immunostimulating Coriolus versicolor extract
-one time intraperitoneal chemotherapy after surgery
might be used (with cisplatin)

Treatment
UNRESECTABLE TUMORS
-chemoradiotherapy reevaluation and if operable=>
surgery
Not operable after chemoradiotherapy:
-obstructive symptoms: palliative gastric resection or
gastro-jejunostomy
-chemotherapy

Helicobacter pylori eradicationmandatory after primary treatment

(for example subtotal gastric
resection)
First line: triple therapy:
-Clarithromycin 3x 500 mg/day
-Amoxicillin 2x1000 mg/day
-Omeprazole 1x20 mg/day
Second line: metronidazole based
regimen
Third line: e. g. Furazolidon

Side effects of gastric

surgery
Total gastrectomy=>loss of intrinsic
factor which binds vitamin B12=>IM
B12 supplementation/PO B12+intrinsic
factor
Some patients can not tolerate
complete gastrectomy: if nutrition is
inadequate they will die of
malnutrition
Dumping syndrome: early and late

Under normal physiologic conditions the stomach controls the rate at

which the gastric contents leave the stomach.
I. Early dumping syndrome: due to quickly filling of the jejunum with
undigested food from the stomach
1. =>bowel distension
2. => movement of water from the blood to the intestine to dilute the
intestinal contents
Symptoms: abdominal bloating, pain/cramping, vomiting, flushing,
sweating, rapid heart rate, light headedness and diarrhea.
II. Late dumping syndrome: hypoglycemia due to increased insulin
secretion as a response to high serum glucose peak
The small bowel is very effective in absorbing sugar, so that the rapid
absorption of a relatively small amount of sugar can cause the glucose
level in the blood to rise rapidly. The pancreas responds to this glucose
challenge by increasing the insulin output. Unfortunately, the sugar
that started the whole cycle was such a small amount that it does not
sustain the increase in blood glucose, which tends to fall back down at
about the time the insulin rush starts.
Symptoms: fatigue, sleepiness

Screening of gastric cancer

In the Western world screening with endoscopy is
low yield
But even here there are high risk groups that may
benefit from stomach cancer screening:
Older people with gastritis or pernicious anemia
Partial gastrectomy
Polyps in the stomach
Genetic predisposing conditions [Familial adenomatous
polyposis (FAP), Hereditary nonpolyposis colon cancer
(HNPCC)]
Immigrants from countries where stomach cancer is
more common.

Screening of gastric cancer

In Asia and other high incidence countries:
screening with endoscopy would be a reasonable
choice if economically sustainable
Screening programs: Japan, South-Korea

Case-control studies suggested a 4060% decrease in

gastric cancer mortality with photofluorography (barium
meal) screening in Japan and Venezuela

Questions
What are the risk factors for gastric cancer?
What are the two main histological types of
gastric cancer and enumerate some
differences.
What are the symptoms of gastric cancer?
What diagnostic tools should be used for
diagnosis of gastric cancer?
What is the main treatment type for gastric
cancer and how it is done?
What is the early and late dumping
syndrome?

Anatomy of
the
esophagus
From the inferior
margin of the
cricopharyngeus
muscle (or from
the inferior
margin of the
cricoid cartilage)
To the cardia of
the stomach
~25 cm in length

Subdivision of the
esophagus

There are two subdivision systems for the

esophagus and they are not equivalent
Subdivision system 1
Cervical-begins at the lower end of pharynx (level of 6th vertebra or lower
border of cricoid cartilage) and extends to the thoracic inlet (suprasternal
notch); 18 cm from incisors.
Thoracic
-Upper thoracic: from thoracic inlet to level of tracheal bifurcation; 18-23 cm.
-Mid thoracic: from tracheal bifuraction midway to gastroesophageal
junction; 24-32 cm.
-Lower thoracic: from midway between tracheal bifurcation and
gastroesophageal junction, including abdominal esophagus; 32-40 cm.
Abdominal-Considered part of lower thoracic esophagus; 32-40 cm.
Subdivision system 2
Upper third (10% of esophageal cancers)
Middle third (40%)
Lower third (50%)

Normal histology
It is lined with stratified
non-keratinizing squamous
epithelium
The lower third (5 to 10 cm) of the
esophagus may contain glandular elements.
Replacement of the stratified squamous
epithelium with columnar epithelium is
referred to as Barrett's esophagus

Normal histology
The lower third (5 to 10 cm) of the
esophagus may contain glandular
elements. Replacement of the
stratified squamous epithelium with
columnar epithelium is referred to as
Barrett's esophagus

Histological subtypes of
esophageal cancer
90% squamous cell carcinoma
10% adenocarcinoma

Epidemiology
Rare cancer in North America and
Europe
High frequency in northern China,
Iran, India and near the Caspian Sea
[alkaline soil, ingestion of nitrosamines and low riboflavin
(=vitamin B2), nicotinic acid, Mg and Zn]

Risk factors for squamous cell

carcinoma

In North America and Western Europe, alcohol

and tobacco use are the major risk factors for
squamous cell carcinoma, accounting for 90%
of cases
Other risk factors:
-HPV infection
-nitrate-rich foods (pickled vegetables, alcoholic
beverages, cured meats and fish)
-Plummer-Vinson (Paterson-Kelly) syndrome=
iron deficiency anemia + low riboflavin;
increased risk for esophageal and oral cavity
+ hypopharyngeal cancers

-achalasia

(failure of the lower esophageal sphincter to

relax during swallowing)

-caustic burns (especially lye corrosion)

-tylosis (hyperkeratosis of the palms and soles and
papilloma of the esophagus)

Risk factors for adenocarcinoma

Barrett's esophagus (caused by
severe and long-standing
gastroesophageal reflux disease
(GERD)
Obesity and hiatal hernia-possibly
due to an increased risk of reflux
Smoking

Extension
DIRECT EXTENSION: No serosa is
present, facilitating extra-esophageal
spread of disease. (The four
esophageal layers: an innermost
epithelial layer, inner circular muscle
layer, an outer longitudinal muscle
layer and an adventitia.)
trachea, bronchia, pleura, lung,
pericardium, large vessels, recurrent
nerves, diaphragm

Extension
Lymphatic spread
-cervical esophagus->upper mediastinal,
inferior cervical, supraclavicular
-thoracic esophagus->mediastinal
-lower thoracic=abdominal esophagus->
mediastinal, celiac
Metastases:
-liver
-lung
-suprarenals
-bone

Clinical features
Dysphagia=difficulty in swallowing
-first for solids, then for liquids
Odynophagia=painful swallowing
Invasion/compression of the trachea:
cough, dyspnea, hemoptisis
Invasion of the recurrent
nerve/nerves: dysphonia
Nonspecific signs and symptoms:
-Weight loss
-Anorexia

Diagnosis and evaluation of

extension

Upper digestive endoscopy with biopsy

Endoscopic US (for evaluation of local
extension and lymph node metastases)
Barium swallow (no indication if endoscopy
is done first)
Head and neck exam (for lymph node
metastases)
CT or better, MRI, or even better PET/CT of
the thorax, cervical region, upper abdomen
General evaluations for an eventual
surgery

PET-CT

Treatment
Tis and T1a (tumor invades lamina
propria)
=>endoscopic mucosal resection
T1bN0 (tumor invades submucosa)
=>esophagectomy
All other loco-regional disease (T1bN1,
T2-T4, N0-N1, M0-M1a):
A) For squamous cell carcinoma:
Chemoradiation -> reevaluation* 5
weeks: persistent disease=>salvage
surgery or boost chemoradiation

*Reevaluation by CT with contrast, PET/CT, endoscopic US, esophageal endoscopy

Treatment
B) For adenocarcinoma:
Chemoradiation -> esophagectomy +
lymphadenectomy

Questions
What are the two main types of
esophageal cancer and what risk factors
do they have?
What are the symptoms of esophageal
cancer?
What is the treatment for locally
advanced esophageal cancer? (Treatment
for both squamous cell carcinoma and
adenocarcinoma should be described.)