Gastrointestinal Cancers: How to recognize them H. Vahedi MD Gastroenterologist

Gastrointestinal Cancers:
How to recognize them
H. Vahedi MD
Gastroenterologist
Associate Professor of Medicine
DDRI
The GI tract, including the:
-hollow organs of the gut
-and pancreas
pancreas, liver
-and biliary tree, is the site of more
cancers
z
z
The cancer epidemiology
p
gy is the wide variabilityy
of tumor incidence from country to country by
organ site
z
For example, an esophageal cancer belt
extends from northeastern China through central
Asia into northern Iran
z
In p
parts of these regions,
g
, the incidence of SCC
of the esophagus is more than 100-fold higher
than that in adjacent low-incidence regions
Esophageal cancer incidence in Central Asia and North Africa
25
20
15
10
5
male
female
0
z
These marked differences in cancer risk are not based on racial or
genetic factors
z
The epidemiological observations strongly indicate the importance of
environmental
i
l ffactors iin GI carcinogenesis
i
i
z
When people migrate:
-from a high incidence region to a low incidence region
-the organ specific rates of some cancers change to match that
of the new region,
g , usually
y within two g
generations
z
However, individual genetic differences may influence the effects of
these factors
Genetic syndromes
z
These include:
z
FAP predisposes sufferers
ff
to CRC
C C as well as
other GI cancers
z
Hereditary hemochromatosis causes too much
iron to accumulate in the liver and increases risk
of liver cancer
z
Hereditary non-polyposis colon cancer(HNPCC)
z
Family history of GI cancers
Conditions that irritate or compromise the GI tract or organs
z
These conditions include:
z
z
z
z
z
z
z
z
z
z
z
z
z
z
z
z
z
Choledochal cysts
Celiac disease
Cirrhosis of the liver
Crohn,s disease
Chronic gastritis
Chronic ulcerative colitis
Fatty liver disease
Gastric polyps
Hepatitis
p
B or hepatitis
p
C infection
Infection with aflatoxin B (through eating contaminated food)
Infection with a Chinese liver fluke parasite
Infection with the Helicobacter pylori bacterium
Inflammatory bowel disease
Intestinal metaplasia
Pancreatitis
Pernicious anemia
Primary sclerosing cholangitis
Symptoms of Gastrointestinal Cancer
z
In general, many of the GI cancers cause few symptoms
until
til th
they h
have advanced
d
d tto a llater
t stage
t
and
d spread
d tto
other organs
z
General symptoms of all GI cancers may include:
-Abdominal pain
-Appetite loss
-Blood
Blood in the stool
-Unexplained fatigue or weakness
-Unexplained weight loss
-Nausea
N
-Vomiting
CLINICAL MANIFESTATIONS OF ESOPHAGEAL CANCER
Dysphagia
z
Both adeno Ca and SCC have similar clinical
presentations except that adeno Ca rises much
more commonly in the distal esophagus/GEJ
z
Obstruction
Ob
t ti off the
th esophagus
h
b
by th
the ttumor causes
progressive solid food dysphagia
z
This usually occurs once the esophageal lumen
diameter is less than 13 mm
Weight loss
-dysphagia
dysphagia
-changes in diet
-and tumor related anorexia
z
Early symptoms of esophageal cancer are subtle and nonspecific
z
Patients may also notice retrosternal discomfort or a burning
sensation
z
Most early (superficial) esophageal cancers in the are detected
serendipitously
z
Regurgitation of saliva or food uncontaminated by gastric
secretions can also occur in patients with advanced disease
z
Aspiration pneumonia is infrequent
z
Hoarseness may occur if the recurrent laryngeal nerve is
invaded
z
Chronic GI blood loss from esophageal cancer is common
and may result in IDA
z
However, patients seldom notice melena, hematemesis or
blood in regurgitated food
z
Acute upper GIB is rare and is a result of tumor erosion into
the aorta or pulmonary or bronchial arteries
z
Tracheobronchial fistulas are a late complication of
esophageal cancer
z
The fistulas are caused by direct invasion through the
esophageal
p g
wall and into the main stem bronchus
z
Such patients often present with intractable coughing or
frequent pneumonias
z
Life expectancy is less than 4 weeks following the
development of this complication
Palmar hyperkeratosis (Tylosis)
z
Keratoderma of the p
palms and soles ((also known as tylosis)
y
)
presents as a yellow, symmetrical, smooth bilateral
thickening of the epidermis
z
The inherited
Th
i h i d type off tylosis
l i (Howell-Evans
(H
ll E
syndrome)
d
)h
has
been most strongly associated with SCC of the esophagus
z
However, sporadic
H
di cases off tylosis
t l i have
h
also
l b
been
associated with:
-Hodgkin lymphoma
-leukemia
leukemia
-and breast cancer
Investigations for patients with gastric cancer
z
BS
z Endoscopy & biopsy
z EUS
z Chest and Abdominal CT
Gastric Cancer
¾
Gastric cancer is one of the most common cancers
worldwide with approximately
pp
y 989,600
,
new cases and
738,000 deaths per year
¾
The incidence of cancer of the stomach continues to decrease
in the United States
S
¾
Sometimes occur in younger people
¾
Men have a higher incidence of gastric cancers than women
¾
The incidence of gastric cancer is much greater in
Japan, which has instituted mass screening programs for
earlier diagnosis
Worldwide prevalence of cancer
Stomach cancer incidence in Central Asia and North Africa
45
40
35
30
25
20
15
female
10
5
0
male
¾
Diet appears to be a significant factor
¾
A diet high in smoked foods and low in fruits and vegetables may
increase the risk of gastric cancer
¾
Other factors related to the incidence of gastric cancer include:
-chronic inflammation of the stomach
-gastric ulcers
-H. pylori infection
-genetics
genetics
-smoking
-and drink alcohol
Pathology
gy
z
Gastric cancer
Adenocarcinoma
z GIST (gastro-intestinal
(gastro intestinal stromal tumour)
z Carcinoid
z Lymphoma
z other
z
Adenocarcinoma
z
Diffuse
Linitis plastica type
z Poorer prognosis
p g
z
z
Intestinal
Localised
z Better prognosis
z Distal stomach
z
Presentation
z
Early cancer
z
z
z
Asymptomatic
Anaemia
Dyspepsia 50%
z
M respond
May
d tto PPI
z
Advanced cancer
z
z
z
z
z
z
z
z
Abdominal pain
Weight loss
Epigastric mass
Ascites
Acanthosis nigricans
Supraclavicular mass
Dysphagia
Jaundice
z
Approximately 25% of patients have a history of GU
z
All gastric ulcers should be followed to complete healing
z
If GU that do not heal should undergo resection
Signs of tumor extension or spread
z
The most common metastatic distribution is to the liver, peritoneal
surfaces
f
(
(ascites)
it )
z
Since gastric cancer can spread via lymphatics, the physical
examination may reveal:
-a left supraclavicular adenopathy (a Virchow's node)
-a periumbilical nodule (Sister Mary Joseph's node)
-a
a left axillary node (Irish node)
z
Peritoneal spread can present with:
-an
an enlarged ovary (Krukenberg's tumor)
-or a mass in the cul-de-sac on rectal examination (Blumer's shelf)
Paraneoplastic manifestations
z
Dermatologic findings may include:
-the sudden appearance of diffuse seborrheic keratosis
-or acanthosis nigricans
z
Neither finding
g is specific
p
for gastric
g
cancer
z
Other paraneoplastic abnormalities that can occur in gastric
cancer include:
i l d
-a microangiopathic hemolytic anemia
-membranous nephropathy
-and
and hypercoagulable states (Trousseau
(Trousseau's
s syndrome)
z
Polyarteritis nodosa has been reported as the single
y and surgically
g
y curable g
gastric cancer
manifestation of an early
Tripe palm
z
Tripe
p p
palm refers to a characteristic velvety
y
thickening of the palms with a ridged or rugose
appearance
z
The term is derived from its resemblance to the
stomach mucosa
z
Tripe palm is predominantly associated with:
-gastric
gastric cancer
-bronchogenic cancer
-and rarely described in other malignancies
Bazex's syndrome
y
z
Bazex's syndrome (acrokeratosis
paraneoplastica) is a rare paraneoplastic
phenomenon
z
Strongly associated with SCC of the upper
aerodigestive tract
z
It has also been reported with a number of
other tumors
Investigations for patients with gastric cancer
z
Endoscopy
py & biopsy
p y
z
CT chest & abdomen
z
EUS (endoscopic ultrasound)
z
Laparoscopy
Referral for endoscopy
z
Routine endoscopy not necessary without alarm
signs
i
!!!
z
Urgent
g
((<2 weeks)) specialist
p
referral for endoscopic
p
investigation when dyspepsia with:
z Chronic GI bleeding
z Progressive w,loss
z Progressive dysphagia
z Persistent vomiting
z Iron deficiency anaemia
z Epigastric mass
z Suspicious barium meal
Referral for endoscopy
z
Indication for endoscopy when symptoms persist
d
despite
it ttreatment
t
t (HP eradication)
di ti ) if patients
ti t h
have:
z
z
z
z
z
z
Prior gastric ulcer
Prior gastric surgery
Need for NSAID usage
Raised gastric cancer risk
Anxiety about cancer
New onset dyspepsia age >55 requires endoscopy
Treatment of gastric cancer
z
Endoscopic
p treatment
z
z
EMR (endoscopic mucosal resection)
Ablation
z
Surgery
z
M lti d l ttreatment
Multimodal
t
t
z
z
z
Neo-adjuvant
Adjuvant
Palliative treatment
Colon Cancer
IBD
1%
Sporadic
80%
Familial
15%
Hereditary
H
dit
4%
CRC Incidence
z
The annual incidence in North America and
Europe is approximately 30–50/100,000
z
This incidence is estimated to be
approximately
pp
y 3–7/100,000
,
in most MiddleEastern countries
Colorectal cancer incidence in Central Asia and North Africa
20
18
16
14
12
10
8
6
4
M l
Male
2
Female
0
GLOBOCAN 2002, IARC
Comparison between colorectal and upper GI cancer incidence in
C
t lA
i A
bi countries
t i and
dN
th Af
i
Central
Asia,
Arabic
North
Africa
25
20
15
10
Upper GI
5
0
Colorectal
CRC epidemiology
p
gy
z
Developing countries have lower rates CRC
particularly
ti l l Af
Africa
i and
dA
Asia
i
z
These geographic differences
ff
appear to be due
to differences in:
-dietary
di t
and
d environmental
i
t l exposures
-background of genetically susceptibility
Risk Factors
One of the most preventable cancers!
Risk increases with age
Nearly 90% of colon cancer patients
are over the age of 50
Risk factors include:
family or personal history of CRC or polyps
chronic inflammatory bowel disease
hereditary colorectal syndromes
use of cigarettes and other tobacco products
high-fat/low fiber diet
physical inactivity
z
Some patients had more than one
abnormality:
-Abdominal
Abd i l pain
i 44%
-Change in bowel habits 43
-Hematochezia or melena 40%
-Weakness 20%
-Anemia without other GI symptoms 11%
-Weight loss 6%
Metastatic disease
z
20% of patients have distant metastatic disease at the time of
presentation
z
CRC can spread by:
-lymphatic
l
h ti and
d hematogenous
h
t
di
dissemination
i ti
-by contiguous and transperitoneal routes
z
The mostt common metastatic
Th
t t ti sites
it are the
th regional
i
l lymph
l
h
nodes, liver, lungs, and peritoneum
z
The presence of RUQ pain,
pain abdominal distention,
distention early
satiety, supraclavicular adenopathy, or periumbilical nodules
usually signals advanced often metastatic disease
Polypectomy Technique
Colon Cancer Testing
The flat polyp
p yp
z
Techniques to improve detection
Narrow band imaging
Narrow-band
z Chromoendoscopy
z Endocytoscopy
z
Soitenko et al. JAMA March 2008
Narrow Band Imaging
g g
Virtual Colonoscopy
z
Spiral CT to generate 3D images
z Cleaning of bowel, distension with air
z Non invasive, no complications
z Not endorsed for CRC screening
Virtual Colonoscopy
py
Limitations Virtual Colonoscopy
z
Variable results
z No screening
g studies
z No longitudinal studies
z Cost
z Does not allow for therapy
Current Recommendations
Average Risk
Test
FOBT
Sigmoidoscopy
FOBT + Sigmoidoscopy
Interval (years)
Yearly
Every 5
Yearly, every 5
C l
Colonoscopy
E
Every
10*
Barium enema
Every
y5
Approach to Colon Cancer Testing
Asymptomatic
Men and Women
Age ≥ 50 yr
Age < 50 yr
No family Hx
YES family Hx
No Screening
HNPCC or FAP
Genetic Counseling
NO family Hx
Average Screening
2 or more first-degree
first degree or
1 first-degree < 60 yrs
Colonoscopy every
5 yrs, starting age 40
1 first
first-degree
degree
≥ 60 yrs
Average risk
Average-risk
screening,
starting age 40
Impact of symptoms on prognosis
-Patients who are symptomatic at diagnosis typically have a worse
p g
prognosis
-In one report, the 5 year survival rate for symptomatic and
asymptomatic patients was 49 versus 71%
-The duration of symptoms is not an accurate predictor of
prognosis
-Obstruction and/or perforation, carry a poor prognosis
-Tumors presenting with hemorrhage have been thought to have a
better prognosis
Reduce Your Risk
Choices for good health
Follow testing guidelines
Know your family history
G t regular
Get
l exercise
i
Do not smoke or use other tobacco products
Avoid excessive alcohol consumption
Reduce Your Risk
Choices for good health
Eat 5 or more servings of fruits & vegetables a day
Choose whole grain foods
Limit your intake of red meat
Maintain a healthy weight
Squatting position for defecation
z
Dr. Burkitt had an alternate theory to explain what
protects
t t the
th developing
d
l i world
ld ffrom colon
l cancer
z
He observed that the natives of Africa and Asia use the
squatting position for defecation
z
This is the posture which all primates were designed to
use and is the only posture in which the lower regions of
use,
the colon (sigmoid, cecum and rectum) can be fully
evacuated
z
These lower regions are where 80% of colorectal cancers
develop
Pancreatic cancer
z
Cancer of the exocrine pancreas is the:
-4
4th or 5th leading
l di cause off cancer-related
l t d
z
The majority of these tumors (85%) are
adenocarcinomas
d
i
arising
i i ffrom th
the d
ductal
t l
epithelium
z
Surgical resection is the only potentially curative treatment
z
Because of the late presentation of the disease, only 15 to 20% of
patients are candidates for pancreatectomy
z
The prognosis of pancreatic cancer is poor even in those with
potentially resectable disease
z
The 5 year survival following pancreaticoduodenectomy is only
about 25 to 30% for node-negative and 10% for node-positive
tumors
z
Incidence rates were approximately 30% higher in men and 50%
higher in blacks compared with whites and people of other races
Risk factors
z
Summarized briefly, the major risk factors include:
-smoking
-hereditary predisposition to pancreatic cancer
-chronic pancreatitis
-diabetes
diabetes
CLINICAL FEATURES
History
z Most patients; weight loss,
loss or jaundice
z Pain is present in 80 to 85% of patients
z The pain is usually felt in the upper abdomen as a dull ache that
radiates straight through to the back
z Weight loss can be profound; it may be associated with anorexia,
early satiety, diarrhea, or steatorrhea
z Jaundice
J
di iis often
ft accompanied
i db
by pruritus,
it
acholic
h li stools,
t l and
dd
dark
k
urine
z Painful jaundice is present in approximately one-half of patients with
l
locally
ll unresectable
t bl disease
di
z Painless jaundice is present in approximately one-half of patients
with a potentially resectable lesion
Physical findings
z
An abdominal mass or ascites can be noted at presentation in patients with
advanced pancreatic cancer
z
A non-tender but palpable gallbladder may be seen or felt at the right costal
margin in those with jaundice
z
Virchow's node or a palpable rectal shelf are present in some patients with
widespread disease
z
Rarely, subcutaneous areas of nodular fat necrosis (pancreatic panniculitis)
may be evident
z
The most common sites of distant metastases include the
liver, peritoneum, lungs, and less frequently, bone
z
Many patients with pancreatic cancer are in a hypercoagulable state
Why are we not diagnosing early cancers despite
improvements
p
in imaging?
g g
z
Patients with early cancers are usually
asymptomatic
z
Early cancers noted in asymptomatic patients are
often overlooked byy radiologists
g
Why renewed emphasis on early diagnosis now?
z
Improved
p
resolution with CT/MRI
z
Advent of EUS-FNA to provide cytologic diagnosis in
patients with early stage pancreatic cancers
z
Advances in molecular testing
z
Better understanding of pathogenesis and natural
history of pancreatic cancer
What speaks against screening?
z
Harm due to screening
Complications
z Overtreatment
z
z
L yield/cost
Low
i ld/
z
No proof that stage migration results in
improved
p
outcome
Is there a good case for screening pancreatic cancer?
ƒ
In ggeneral p
population?
p
-Incidence is 1 in 100,000
ƒ
In high risk patient groups?
-New onset diabetes mellitus
-Idiopathic
d
h acute pancreatitis in the
h elderly
ld l
-New diagnosis of chronic pancreatitis
-New
New onset unipolar depression in the elderly
Which tests are best potential candidates for
pancreatic cancer screening
1.
2.
3
3.
4.
5
5.
6.
Serum markers
Cross sectional imaging with spiral CT or MRI
EUS/FNA
ERCP
Abdominal US
None of the above