Prevention of GI malignancy

G N RameshPVS Memorial Hospital

Cochin

Schema

• Principles of prevention• H pylori and gastric cancer – should we eradicate

in all?• Barrett’s and malignancy – do we need to bother?• Hepatitis virus and liver cancers – how could we

do more?• Colonic cancers – applying guidelines to our

population • Pancreatic cancer – we know the preneoplastic

situations .. But can we prevent?

Principles of prevention

• Primary – preventing the intitiation of the carcinogenic process – elimination , avoiding or neutralising the carcinogen

• Secondary – interfering with the metabolism of carcinogen or preventing it from reaching the target ( tissue DNA)

• Tertiary – preventing precancerous lesions from progressing to cancer ( surveillance)

My aim

• Summary of factors that can be changed in our population to decrease and prevent GI cancers

My aim

• Summary of factors that can be changed in our population to decrease and prevent GI cancers

30% of cancer deaths are due to 5 behavioral risk factors

High BMIReduced intake of fruits/vegetables

Sedentary life styleSmoking

Alcohol use

Gastric cancer

The premalignant conditions

• Chronic atrophic gastritis• Intestinal metaplasia• H pylori• Gastric adenoma

Gastric carcinogenesis: Histologic changes from normal gastric mucosa to neoplasia

Two ends of a spectrum

• Proximal cancers

• GERD• Obesity

• Distal cancers

• Dietary factors• H pylori

Primary prevention

• Decreased salt intake• Increased vitamin C consumption• Quit smoking• H pylori eradication – class I carcinogen –

decreased Ca by 35%

The metanalysis

The final word?

• 1.8% vs 2.4% in controls• NNT – 15 for Chinese , 245 for USA ,• India?

Adenocarcinoma of the Esophagus

Gastroesophageal reflux/Barrett esophagus

• Association exists between gastroesophageal reflux disease (GERD) and adenocarcinoma – duration and severity.

• Does elimination of gastroesophageal reflux by surgical or medical means reduce the risk of adenocarcinoma of the esophagus ???

• RFA of Barrett esophagus with severe dysplasia may lead to eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression

• When should you ablate? HGD or early adenoca…..not metaplasia

• Does ablation reduce adenoca ? Perhaps yes• Does surgery reduce adenoca? .. Series of

Swedish reports – no!• Do we need surveillance in India? – no

evidence.

Hepatitis and liver cancer

Causes

• HBV and HCV – 80% of cases• Cirrhosis• Alcohol• Steatosis and diabetes• Medications/toxins• Genetic / metabolic diseases

The impact of vaccination on liver cancer

The Taiwan experience

Success of Hepatitis B vaccine

Other issues

• Antivirals and the impact on carcinogenesis – not recurrence

• Improving the efficacy of screening programs• Effective modification of the modifiable

factors

HCV and liver cancer

• Safe practices to prevent HCV• New age antivirals and their potential impact

on carcinogenesis

NAFLD , cirrhosis and cancer

Non modifiable modifiable

The final word…

• We can do lots more • We aren’t doing enough.• Education and awareness are the key

Colon cancer

Who is at risk?

• Age -> 50 yrs ( 90% of all CRCs)• History

first degree relative ( < 55 yrs at diagnosis) doubles the risk personal h/o CRC / high risk adenomas/ovarian ca

• Others – IBD , genetic ( hereditary GI cancer) , HNPCC , FAP

Factors and interventions to decrease CRC

Increased riskAlcohol – RR 1.41 > 45g/d

Smoking – RR 1.18Obesity – RR 1.45 BMI>29

Decreased riskPhysical activity 24% reduction

Factors and interventions to decrease CRC

Increased riskAlcohol – RR 1.41 > 45g/d

Smoking – RR 1.18Obesity – RR 1.45 BMI>29

Decreased riskPhysical activity 24% reduction

InterventionsNSAIDsAspirin

Physical ActivityHormones – estrogen-progestin combination

High fiber, fruits , vegetables – inadequate evidenceLow fat/meat – inadequate evidence

Calcium supplementation – no evidenceStatins – insufficient evidence

When to start?

• Average risk – 50 yrs• Moderate risk – ( Blacks , MS , abdominal

obesity ) 45 yrs• High risk – familial - earlier

How often after polyp detection?

• Small rectal polyps – 10 yrs• 1 or 2 small (<1 cm) with LGD – 5-10 YRS• 3 or more adenomas , > 1 cm , villous/HGD – 3 yrs• 10 or more - 3 yrs• Sessile polyps / piecemeal removal / HGD – 2-6 mos• HNPCC/FAP – more intensive

How often after polyp detection?

• Small rectal polyps – 10 yrs• 1 or 2 small (<1 cm) with LGD – 5-10 YRS• 3 or more adenomas , > 1 cm , villous/HGD – 3 yrs• 10 or more - 3 yrs• Sessile polyps / piecemeal removal / HGD – 2-6 mos• HNPCC/FAP – more intensive

HOW EFFECTIVE IS IT?Prevents 85% of cases of distal CRC ; less effective for proximal CRC

26% reduction of mortality with flexible sigmoidoscopyRisk reduces with removal of polyps > 1 cm ; not proven with polyps <

1 cm

Prevention of colorectal ca

• Diet, exercise, smoking, and supplements• daily aspirin may decrease the risk of

colorectal and extracolonic cancer in LS, currently the evidence is not sufficiently robust (CAPP1 , CAPP2 , CAPP3 trials)

The final word….

• Guidelines well established• Putting guidelines into practice…not well

established• Awareness , education , enforcement• Whom? When ? What frequency ? For India

Pancreatic cancer

• Lethal• Stage at diagnosis• Lack of effective medical therapy• No effective screening methods• Primary prevention – most effective way to

reduce burden

19 prospective studies ; 3 meta analyses10-45% increase for every 5 BMI

Stronger association with obesity in the young ( 30-40 yrs)

? Related to pancreatic steatosisObesity and diabetes – risk cumulative

Who is at risk for adenoca?

• Genetic syndromes - hereditary breast–ovarian cancer syndrome, familial atypical multiple melanoma and mole syndrome (FAMMM), PJS, LS, or other gene mutations

• Three or more relatives with pancreatic cancer

• Hereditary pancreatitis.

HOW?

• Surveillance for PC should be with endoscopic ultrasound and/or MRI of the pancreas annually starting at age 50 years, or 10 years younger than the earliest age of PC in the family.

• Patients with PJS should start surveillance at age 35 years

Screening tools ..and I whom?

• No guidelines• Chronic pancreatitis; hereditary

pancreatic cancer; hereditary pancreatitis

• How? MRI/EUS

Jack Andraka, the Teen Prodigy of Pancreatic Cancer

A high school sophomore won the youth achievement Smithsonian American Ingenuity Award for inventing a new method to detect a

lethal cancerhe won the $75,000 grand prize at this past spring’s Intel International

Science and Engineering Fair,“Edison of our times,”

Follow us: @SmithsonianMag on Twitter

Conclusions

• Sound knowledge of factors associated with GI cancer

• Interventions need to be executed• Awareness and education is the key• Common risk factors – smoking , obesity ,

diets , physical inactivity , alcohol – reduced burden by 25-40%

• HBV,HCV – another 10-15%

FAP

Esophageal cancers • The following risk factors may increase the

risk of esophageal cancer:– Tobacco and alcohol use– Gastric reflux and Barrett esophagus

• The following protective factors may decrease the risk of esophageal cancer:– Avoiding tobacco and alcohol use– Diet– Nonsteroidal anti-inflammatory drugs– Radiofrequency ablation.

• Screening for gastric and proximal small bowel tumors should be done using upper GI endoscopy including duodenoscopy starting at age 25–30 years.

• Annual thyroid screening by ultrasound should be recommended to individuals affected with FAP, MAP, and attenuated polyposis

Hereditary gastric cancer

• (i) ≥2 cases of diff use gastric cancer, with at least one diagnosed at <50 years,

• (ii) ≥3 cases of documented diffuse cancer in first- or second-degree relatives independent of age of onset;

• (iii) diffuse gastric cancer diagnosed at <40 years; and• (iv) a personal or family history of diffuse gastric cancer

and lobular breast cancer with one diagnosed at <50 years should be evaluated for hereditary diffuse gastric cancer.

Management

• (i) prophylactic gastrectomy after age 20 years (>80% risk by age 80 years);

• (ii) breast cancer surveillance in women beginning at age 35 years with annual mammography and breast MRI and clinical breast examination every 6 months,

• (iii) colonoscopy beginning at age 40 years for families that include colon cancer