Download Stomach and esophageal cancer

1. Stomach and
2. esophageal cancer
Stomach cancer-Anatomy
• Parts of the stomach:
-cardia (cardiac portion)
-fundus
-body
-pyloric antrum
-pyloric canal
1. CARDIAC PORTION
2. FUNDUS
3. BODY
5. PYLORIC CANAL
4. (PYLORIC) ANTRUM
PYLORIC PORTION
-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
• It’s 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-Lauren’s 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
a) 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-Bormann’s classification
•
•
•
•
•
•
Bormann type 1: polypoid or protuberant
carcinoma (usually a well-differentiated
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 signetring cell metastasis on the ovary from
gastrointestinal or breast cancers)
• Blumer’s 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 gastrojejunostomy
-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 40–60% 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.)