Gastrointestinal Cancers:Gastrointestinal Cancers:

How to recognize them

H. Vahedi MD

Gastroenterologist

Associate Professor of Medicine

DDRI

The GI tract, including the:The GI tract, including the:-hollow organs of the gut-and pancreas liver-and pancreas, liver-and biliary tree, is the site of more

cancerscancers

The cancer epidemiology is the wide variability p gy yof tumor incidence from country to country by organ site

For example, an esophageal cancer belt extends from northeastern China through central Asia into northern IranAsia into northern Iran

In parts of these regions, the incidence of SCC p g ,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

15

20

5

10

male

0

5 male

female

These marked differences in cancer risk are not based on racial or genetic factorsgenetic factors

The epidemiological observations strongly indicate the importance of i l f i GI i ienvironmental factors in GI carcinogenesis

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, usually within two generations g , y g

However, individual genetic differences may influence the effects of these factorsthese factors

Genetic syndromes

These include:ff C CFAP predisposes sufferers to CRC as well as

other GI cancers

Hereditary hemochromatosis causes too much iron to accumulate in the liver and increases risk of liver cancerof liver cancer

Hereditary non-polyposis colon cancer(HNPCC)

Family history of GI cancers

Conditions that irritate or compromise the GI tract or organs

These conditions include:Choledochal cystsCeliac diseaseCirrhosis of the liverCrohn,s diseaseChronic gastritisChronic ulcerative colitisFatty liver diseaseGastric polypsHepatitis B or hepatitis C infectionp pInfection with aflatoxin B (through eating contaminated food)Infection with a Chinese liver fluke parasiteInfection with the Helicobacter pylori bacteriumInflammatory bowel diseaseInflammatory bowel diseaseIntestinal metaplasiaPancreatitisPernicious anemiaPrimary sclerosing cholangitisPrimary sclerosing cholangitis

Symptoms of Gastrointestinal Cancer

In general, many of the GI cancers cause few symptoms til th h d d t l t t d d tuntil they have advanced to a later stage and spread to

other organs

General symptoms of all GI cancers may include:General symptoms of all GI cancers may include:-Abdominal pain-Appetite lossBlood in the stool-Blood in the stool

-Unexplained fatigue or weakness-Unexplained weight lossN-Nausea

-Vomiting

CLINICAL MANIFESTATIONS OF ESOPHAGEAL CANCERCLINICAL MANIFESTATIONS OF ESOPHAGEAL CANCER

Dysphagia

Both adeno Ca and SCC have similar clinical presentations except that adeno Ca rises muchpresentations except that adeno Ca rises much more commonly in the distal esophagus/GEJ

Ob t ti f th h b th tObstruction of the esophagus by the tumor causes progressive solid food dysphagia

This usually occurs once the esophageal lumen diameter is less than 13 mm

Weight loss dysphagia-dysphagia

-changes in diet-and tumor related anorexia

Early symptoms of esophageal cancer are subtle and nonspecific

Patients may also notice retrosternal discomfort or a burning sensation

Most early (superficial) esophageal cancers in the are detected serendipitously

Regurgitation of saliva or food uncontaminated by gastric secretions can also occur in patients with advanced diseasesecretions can also occur in patients with advanced disease

Aspiration pneumonia is infrequent

Hoarseness may occur if the recurrent laryngeal nerve is invaded

Chronic GI blood loss from esophageal cancer is common and may result in IDA

However, patients seldom notice melena, hematemesis or blood in regurgitated food

Acute upper GIB is rare and is a result of tumor erosion into the aorta or pulmonary or bronchial arteriesthe aorta or pulmonary or bronchial arteries

Tracheobronchial fistulas are a late complication of esophageal canceresophageal cancer

The fistulas are caused by direct invasion through the esophageal wall and into the main stem bronchusp g

Such patients often present with intractable coughing or frequent pneumonias

Life expectancy is less than 4 weeks following the development of this complication

Palmar hyperkeratosis (Tylosis)

Keratoderma of the palms and soles (also known as tylosis) p ( y )presents as a yellow, symmetrical, smooth bilateral thickening of the epidermis

Th i h i d f l i (H ll E d ) hThe inherited type of tylosis (Howell-Evans syndrome) has been most strongly associated with SCC of the esophagus

H di f t l i h l bHowever, sporadic cases of tylosis have also been associated with:

-Hodgkin lymphomaleukemia-leukemia

-and breast cancer

Investigations for patients with gastric cancer

BSBSEndoscopy & biopsyEUSEUSChest and Abdominal CT

Gastric Cancer

Gastric cancer is one of the most common cancers worldwide with approximately 989,600 new cases and pp y ,738,000 deaths per year

The incidence of cancer of the stomach continues to decrease Sin the United States

Sometimes occur in younger people

Men have a higher incidence of gastric cancers than women

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

30

35

40

15

20

25

female

0

5

10female

male

Diet appears to be a significant factor

A diet high in smoked foods and low in fruits and vegetables may increase the risk of gastric cancer

Other factors related to the incidence of gastric cancer include:-chronic inflammation of the stomach-gastric ulcers-H. pylori infectiongenetics-genetics

-smoking-and drink alcohol

Pathologygy

Gastric cancerGastric cancerAdenocarcinomaGIST (gastro intestinal stromal tumour)GIST (gastro-intestinal stromal tumour)CarcinoidLymphomaLymphomaother

Adenocarcinoma

DiffuseLinitis plastica typePoorer prognosisp g

IntestinalIntestinalLocalisedBetter prognosisBetter prognosisDistal stomach

Presentation

Early cancerAsymptomatic

Advanced cancerAbdominal pain

AnaemiaDyspepsia 50%

M d t PPI

Weight lossEpigastric mass

May respond to PPI AscitesAcanthosis nigricansSupraclavicular massSupraclavicular massDysphagiaJaundiceJaundice

Approximately 25% of patients have a history of GU

All gastric ulcers should be followed to complete healing

If GU that do not heal should undergo resection

Signs of tumor extension or spreadSigns of tumor extension or spread

The most common metastatic distribution is to the liver, peritoneal f ( it )surfaces (ascites)

Since gastric cancer can spread via lymphatics, the physical examination may reveal:examination may reveal:

-a left supraclavicular adenopathy (a Virchow's node) -a periumbilical nodule (Sister Mary Joseph's node)a left axillary node (Irish node)-a left axillary node (Irish node)

Peritoneal spread can present with:an enlarged ovary (Krukenberg's tumor)-an enlarged ovary (Krukenberg's tumor)

-or a mass in the cul-de-sac on rectal examination (Blumer's shelf)

Paraneoplastic manifestationsParaneoplastic manifestations

Dermatologic findings may include:-the sudden appearance of diffuse seborrheic keratosis-the sudden appearance of diffuse seborrheic keratosis-or acanthosis nigricans

Neither finding is specific for gastric cancerg p g

Other paraneoplastic abnormalities that can occur in gastric i l dcancer include:

-a microangiopathic hemolytic anemia-membranous nephropathyand hypercoagulable states (Trousseau's syndrome)-and hypercoagulable states (Trousseau s syndrome)

Polyarteritis nodosa has been reported as the single manifestation of an early and surgically curable gastric cancery g y g

Tripe palm

Tripe palm refers to a characteristic velvety p p ythickening of the palms with a ridged or rugoseappearance

The term is derived from its resemblance to the stomach mucosa

Tripe palm is predominantly associated with:-gastric cancergastric cancer-bronchogenic cancer-and rarely described in other malignancies

Bazex's syndromey

Bazex's syndrome (acrokeratosisparaneoplastica) is a rare paraneoplasticphenomenonphenomenon

Strongly associated with SCC of the upperStrongly associated with SCC of the upper aerodigestive tract

It has also been reported with a number of other tumors

Investigations for patients with gastric cancer

Endoscopy & biopsypy p y

CT chest & abdomen

EUS (endoscopic ultrasound)

Laparoscopy

Referral for endoscopyReferral for endoscopy

Routine endoscopy not necessary without alarm i !!!signs !!!

Urgent (<2 weeks) specialist referral for endoscopic g ( ) p pinvestigation when dyspepsia with:

Chronic GI bleedingProgressive w,lossProgressive w,lossProgressive dysphagiaPersistent vomitingIron deficiency anaemiaIron deficiency anaemiaEpigastric massSuspicious barium meal

Referral for endoscopy

Indication for endoscopy when symptoms persist d it t t t (HP di ti ) if ti t hdespite treatment (HP eradication) if patients have:

Prior gastric ulcerPrior gastric surgeryNeed for NSAID usageRaised gastric cancer riskAnxiety about cancerAnxiety about cancer

New onset dyspepsia age >55 requires endoscopy

Treatment of gastric cancer

Endoscopic treatmentpEMR (endoscopic mucosal resection)Ablation

Surgery

M lti d l t t tMultimodal treatmentNeo-adjuvantAdjuvant

Palliative treatment

Colon Cancer

IBD1%

Familial15%

Sporadic80%

1%

15%

H dit

80%

Hereditary4%

CRC Incidence

The annual incidence in North America andThe annual incidence in North America and Europe is approximately 30–50/100,000

This incidence is estimated to be approximately 3–7/100,000 in most Middle-pp y ,Eastern countries

Colorectal cancer incidence in Central Asia and North Africa

20

12

14

16

18

4

6

8

10

M l

0

2

4 Male

Female

GLOBOCAN 2002, IARC

Comparison between colorectal and upper GI cancer incidence in C t l A i A bi t i d N th Af iCentral Asia, Arabic countries and North Africa

25

20

10

15

0

5

Upper GI

Colorectal

0

CRC epidemiologyp gy

Developing countries have lower rates CRC ti l l Af i d A iparticularly Africa and Asia

ffThese geographic differences appear to be due to differences in:

di t d i t l-dietary and environmental exposures -background of genetically susceptibility

Risk FactorsRisk FactorsOne of the most preventable cancers!

Risk increases with age

Nearly 90% of colon cancer patientsare over the age of 50

Nearly 90% of colon cancer patientsare over the age of 50

Risk factors include:

family or personal history of CRC or polyps

Risk factors include:

family or personal history of CRC or polypsfamily or personal history of CRC or polypschronic inflammatory bowel diseasehereditary colorectal syndromesuse of cigarettes and other tobacco products

family or personal history of CRC or polypschronic inflammatory bowel diseasehereditary colorectal syndromesuse of cigarettes and other tobacco productsuse of cigarettes and other tobacco productshigh-fat/low fiber dietphysical inactivity

use of cigarettes and other tobacco productshigh-fat/low fiber dietphysical inactivity

Some patients had more than one abnormality:

Abd i l i 44%-Abdominal pain 44%-Change in bowel habits 43-Hematochezia or melena 40%-Weakness 20%-Anemia without other GI symptoms 11%-Weight loss 6%

Metastatic disease

20% of patients have distant metastatic disease at the time of presentationpresentation

CRC can spread by:l h ti d h t di i ti-lymphatic and hematogenous dissemination

-by contiguous and transperitoneal routes

Th t t t ti it th i l l hThe most common metastatic sites are the regional lymph nodes, liver, lungs, and peritoneum

The presence of RUQ pain abdominal distention earlyThe presence of RUQ pain, abdominal distention, early satiety, supraclavicular adenopathy, or periumbilical nodules usually signals advanced often metastatic disease

Polypectomy Technique

Colon Cancer Testing

The flat polypp yp

Techniques to improve detectionNarrow-band imagingNarrow band imagingChromoendoscopyEndocytoscopyEndocytoscopy

Soitenko et al. JAMA March 2008

Narrow Band Imagingg g

Virtual Colonoscopy

Spiral CT to generate 3D imagesCleaning of bowel, distension with airCleaning of bowel, distension with airNon invasive, no complicationsNot endorsed for CRC screeningNot endorsed for CRC screening

Virtual Colonoscopypy

Limitations Virtual ColonoscopyLimitations Virtual ColonoscopyLimitations Virtual Colonoscopy Limitations Virtual Colonoscopy

Variable resultsNo screening studiesgNo longitudinal studiesCostCostDoes not allow for therapy

Current RecommendationsAverage RiskAverage Risk

Test Interval (years)FOBT YearlyFOBT Yearly

Sigmoidoscopy Every 5

FOBT + Sigmoidoscopy Yearly, every 5

C l E 10*Colonoscopy Every 10*

Barium enema Every 5 y

Approach to Colon Cancer Testing

AsymptomaticMen and Women

Age < 50 yr Age ≥ 50 yr

No family Hx YES family Hx NO family Hx

No Screening

HNPCC FAP 1 first-degree2 or more first-degree or

Average Screening

HNPCC or FAP 1 first degree≥ 60 yrs

Average-risk

2 or more first degree or 1 first-degree < 60 yrs

Genetic CounselingAverage riskscreening,

starting age 40

Colonoscopy every5 yrs, starting age 40

Impact of symptoms on prognosis

-Patients who are symptomatic at diagnosis typically have a worse prognosisp g

-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 RiskReduce Your RiskReduce Your RiskReduce Your RiskChoices for good health

Follow testing guidelinesFollow testing guidelines

Know your family history

G t l i

Know your family history

G t l iGet regular exercise

Do not smoke or use other tobacco products

Get regular exercise

Do not smoke or use other tobacco products

Avoid excessive alcohol consumptionAvoid excessive alcohol consumption

Reduce Your RiskReduce Your RiskReduce Your RiskReduce Your RiskChoices for good health

Eat 5 or more servings of fruits & vegetables a day

Choose whole grain foods

Eat 5 or more servings of fruits & vegetables a day

Choose whole grain foodsChoose whole grain foods

Limit your intake of red meat

Choose whole grain foods

Limit your intake of red meat

Maintain a healthy weight Maintain a healthy weight

Squatting position for defecation

Dr. Burkitt had an alternate theory to explain what t t th d l i ld f lprotects the developing world from colon cancer

He observed that the natives of Africa and Asia use the squatting position for defecationsquatting position for defecation

This is the posture which all primates were designed to use and is the only posture in which the lower regions ofuse, and is the only posture in which the lower regions of the colon (sigmoid, cecum and rectum) can be fully evacuated

These lower regions are where 80% of colorectal cancers develop

Pancreatic cancer Cancer of the exocrine pancreas is the:

4th 5th l di f l t d-4th or 5th leading cause of cancer-related

The majority of these tumors (85%) are d i i i f th d t ladenocarcinomas arising from the ductal

epithelium

Surgical resection is the only potentially curative treatment

Because of the late presentation of the disease, only 15 to 20% of patients are candidates for pancreatectomy

The prognosis of pancreatic cancer is poor even in those with potentially resectable disease

The 5 year survival following pancreaticoduodenectomy is only about 25 to 30% for node-negative and 10% for node-positive tumors

Incidence rates were approximately 30% higher in men and 50% higher in blacks compared with whites and people of other races

Risk factors

Summarized briefly, the major risk factors include:-smoking-hereditary predisposition to pancreatic cancer -chronic pancreatitis diabetes-diabetes

CLINICAL FEATURES

HistoryMost patients; weight loss or jaundiceMost patients; weight loss, or jaundice Pain is present in 80 to 85% of patientsThe pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the backradiates straight through to the backWeight loss can be profound; it may be associated with anorexia, early satiety, diarrhea, or steatorrheaJ di i ft i d b it h li t l d d kJaundice is often accompanied by pruritus, acholic stools, and dark urinePainful jaundice is present in approximately one-half of patients with l ll t bl dilocally unresectable diseasePainless jaundice is present in approximately one-half of patients with a potentially resectable lesion

Physical findingsPhysical findings

An abdominal mass or ascites can be noted at presentation in patients with advanced pancreatic cancer

A non-tender but palpable gallbladder may be seen or felt at the right costal margin in those with jaundice

Virchow's node or a palpable rectal shelf are present in some patients with widespread disease

Rarely, subcutaneous areas of nodular fat necrosis (pancreatic panniculitis) may be evident

The most common sites of distant metastases include theThe most common sites of distant metastases include the liver, peritoneum, lungs, and less frequently, bone

Many patients with pancreatic cancer are in a hypercoagulable state

Why are we not diagnosing early cancers despite improvements in imaging?p g g

Patients with early cancers are usually Patients with early cancers are usually asymptomatic

Early cancers noted in asymptomatic patients are often overlooked by radiologistsy g

Why renewed emphasis on early diagnosis now?

Improved resolution with CT/MRIp

Advent of EUS-FNA to provide cytologic diagnosis in patients with early stage pancreatic cancers

Advances in molecular testing Advances in molecular testing

Better understanding of pathogenesis and natural Better understanding of pathogenesis and natural history of pancreatic cancer

What speaks against screening?

Harm due to screeningHarm due to screeningComplications

OvertreatmentOvertreatment

L i ld/Low yield/cost

No proof that stage migration results in improved outcomep

Is there a good case for screening pancreatic cancer?

In general population?g p p

-Incidence is 1 in 100,000

In high risk patient groups?

-New onset diabetes mellitus

d h h ld l-Idiopathic acute pancreatitis in the elderly

-New diagnosis of chronic pancreatitis

New onset unipolar depression in the elderly-New onset unipolar depression in the elderly

Which tests are best potential candidates for pancreatic cancer screeningpancreatic cancer screening

1. Serum markers1. Serum markers

2. Cross sectional imaging with spiral CT or MRI

3 EUS/FNA3. EUS/FNA

4. ERCP

5 Abdominal US5. Abdominal US

6. None of the above