gastric cancer labs: hb 7.4, microcytic for the early ... · pdf fileslide 1 screening and...

Screening and Surveillance for the Early Detection of

Gastric Cancer

Society of Gastroenterology Nurses and Associates

April 11, 2015

Salina Lee, MD

Assistant Professor of Medicine

Division of Digestive Diseases

Rush University Medical Center

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Slide 2 Case FG

• 63 year old African American male admitted for fatigue

• PMHx: HTN, GERD

• Meds: antiHTN, PPI

• FHx: noncontributory

• SocHx: grew up in Chicago, social EtOH, never tobacco

• ROS: (+) weight loss -~20lbs/3-4 months

• Exam unremarkable

• Labs: Hb 7.4, microcytic

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Slide 3 Endoscopy

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How could this happen…

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Slide 5

GASTRIC CANCER

Screening and surveillance for the early detection of

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Slide 6 Background

• Gastric cancer 4th most common cancer in the world

• 937,00 new cases per year, accounting for nearly 10% of all

new cancers

• 2nd highest cause of cancer-related deaths worldwide

700,000 deaths per year

• Wide global variation 2/3 cases in developing countries

Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201de Vries AC et al. Helicobacter2007;12:1-15deVries AC and Kuipers EJ. Helicobacter 2007;12:22-31

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Mechanism

• Mechanism of gastric carcinogenesis complicated and largely unknown

• Majority is associated with histologically recognizable premalignant stages first described by Pelayo Correa in mid 1970’s

• Chronic H. pylori infection is thought to initiate a premalignant cascade

• Sequence involves chronic superficial gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and invasive neoplasia

Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201

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Slide 8

Sudan 2.5

China 41.3

Japan 46.8

US5.7

Netherlands 8.6

Globocan 2008: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5 version 2.0, IARC Press 2008Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201de Vries AC et al. Helicobacter2007;12:1-15

Of note, it is not clearly associated with the developing world – eg: Africa

China 50

Japan 93

•In the “west,” though incidence is low, mortality remains high because index of suspicion is low•Late diagnosis 5 yr survival <20% •Early detection 5 yr survival as high as 90%

Burden of Disease High incidence•East Asia•Central America •South America

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Slide 9

• Benefits of surveillance has been evaluated and known

• H. pylori should be treated if found

• If low grade dysplasia is detected, surveillance EGD with

topographic mapping

• For US, the progression of IM to cancer is low and

surveillance is not indicated for the average risk patient

ASGE guideline: the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. GIE 2006;63: 570-580

ASGE Guidelines

Who is considered higher than “average risk”?

What could be done before “dysplasia?” at the point of “intestinal metaplasia”

How and who should be tested for H. pylori?

UNANSWERED QUESTIONS

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RISK FACTORS FOR GASTRIC CANCER

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Slide 11 Risk Factors

Habitat

• Smoking

• Nitrate high diet

• Low fresh fruit and vegetables

• Alcohol use

Host

• low socioeconomic class

• blood group A

• familial occurrence of gastric cancer

H. pylori• H. pylori virulence

• Host genetics

• Interaction

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Slide 12

• Cigarette smoking

• HPV

• HCV

Screen for class 1 carcinogens

• H. Pylori

• The most successful human pathogen

• ~50% human population infected

We don’t screen …

Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201deVries AC and Kuipers EJ. Helicobacter 2007;12:22-31Malfertheiner P et al. Gut 1012; 61:646-664

1980s• H. pylori discovered

1994• NIH consensus conference recognized HP as a cause of gastric and

duodenal ulcers

1994

• International Agency for Research on Cancer (IARC) and World Health Organization (WHO) classified H. pylori as a Class I (definite) human carcinogen

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genetic

environsbacterial

non-neoplastic malignancy

Complicated interrelationship

Majority of the course is benign

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Slide 14 East vs. West

de Vries AC et al. Helicobacter2007;12:1-15

The pattern to notice: When HP (+) higher incidence of AG or IM regardless of world region

HP 40%

(+)

AG: to 60%

IM: 40-50%

(-)

AG: 5-10%

IM: 5-10%

HP 60%

(+)

AG: 80%

IM: 40%

(-)

AG: 10%

IM: 5%

Issue of geography…Japan Western Europe

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Slide 15

Gut 2001;49:347-353Kim N et al. J Clin Gastroenterol 2008;42:448-454Rokkas T et al. Helicobacter 2007;12:32-38

2001: 12 case control studies within prospective cohorts•H. Pylori positivity increases risk of developing gastric cancer 6 fold

2008: Prospective study over 9.4 years•Patients infected with h. pylori have 10.9 fold higher chance of gastric cancer than uninfected

2007: Meta-analysis f/u long term impact of HP eradication on gastric ca risk•8 studies, 10-137 months f/u •IM may be a point of no return where progression to gastric cancer is inevitable•Suggests HP eradication should precede onset of metaplastic lesions

Argument for screening for H.Pylori

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H. Pylori screening

Gastric MALT lymphoma

Active peptic ulcer disease

Past history of documented peptic ulcer

Test and treat for dyspepsia

(<55yo and no alarm symptoms)

Kalaghchi B et al. J Clin Gastroenterol 2004;38:248-51

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Slide 17 H. Pylori screening

Patients who are on ppi longterm

Prior to treatment with NSAIDs

Unexplained iron deficiency anemia

Unexplained vitamin b12 deficiency

*Assymptomatic not tested

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Slide 18 New recommendations

Talley NJ et al. Gastric cancer consensus conference recomends Helicobacter pylori screening and treatment in asymptomatic persons from high-risk populations to prevent gastric cancer. AJG 2008;103:510Malfertheiner P et al. Management of Helicobacter pylori infection – the Maastricht IV/Florence Consensus Report. Gt 2012;61:646Chey WD et al. Practice Parameters Committee of the ACG. ACG guideline on the management of Heliocbacter pylori infection. AJG 2007;102:1808

Asian pacific guidelines

• Population based screening for high risk groups

European guidelines

• Population based screening for high risk groups

ACG guidelines

• Describe high risk populations but consider strategies for screening such groups as controversial

WHO to screen

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Case FG

• Endoscopy:• Urea breath test:

– negative

• Pathology: – Mass: invasive

adenocarcinoma

– Random: atrophic gastritis and multiple foci of intestinal metaplasia involving the antrum and corpus of the stomach

– H. pylori negative

No H. pylori?...

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Slide 20 Choosing the right test

Clinical settingPretest

probability

Sensitivity and specificity

Cost effectiveness

and availability

Gatta l. Am J Gastro 2004;99:823

HOW to screen

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Slide 21

Rapid UreaseTest

• Hydrolysis of urea

• Sens 90-95%

• Spec 95-100%

Histology

•Sens >95%•Spec >95%•Limited by cost, not usually needed

Culture

• Only for sensitivity in refractory disease

Endoscopic testing

Chey W et al. Am J Gastroenterol 2007;102:1808-1825

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Non-invasive testing

Breath urea


• Sens 88-95%

• Spec 95-100%

Stool Ag

• Detects HP via enzyme immunoassay

• Sens 94%

• Spec 86-92%

Serology

Gatta l. Am J Gastro 2004;99:823Malfertheiner P et al. Gut 1012; 61:646-664

•Recommended as test of choice•Most accurate noninvasive test for active HPI

False negatives

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Slide 23 Watch out for false negatives

Decreased sensitivity


Meds Blood Mucosa

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Slide 24 Mechanism of decreasing sensitivity

- increase in gastric pH

- rise in periplasmic pH in HP

- decreases internal urease activity

- decrease bacterial density

- may be responsible for decreased sensitivity in both tests


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• Aim: to determine if sensitivity of Urea Breath Test (UBT) and H. pylori Stool Antigen Test (HpSA) is decreased with PPI

• Prospective single blind randomized study

• n=152 patients/6 mo with h. pylori infection

• HP infection

– rapid urease (+) and histology

– or culture (+) alone


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Slide 26

2 weeks treatment2 weeks treatment2 weeks treatment

n=24AlOH 800mg/d

n=24 esomeprazole 40mg/d

n=24 omeprazole 20/d

n=72 enrolled

n=152 eligible

HpSAUBT HpSAUBTHpSAUBT

Stool TestUBTStool TestStool TestUBT UBT


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Slide 27 Results


Baseline

After treatment

Sensitivity: UBT

72.9-85.4%

AntacidPPI

Stool Test

Antacid PPI

100% 100% 90.0%97.8%

83.0%100% 90.0%

Conclusion: PPI decreases sensitivity of UBT and HpSAAntacid will not alter sensitivity of UBT or HpSA

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And Ranitidine or Bismuth?

Gatta l. Am J Gastro 2004;99:823Laine L et al. 1998 / Manes G et al. 2001 / Bravo L et al. 1999Parente F et al / Connor S et al 1999 / Dulbecco P et al. 2003 / Savarino V et al. 2000Savarino V et al. Am J Gastroenterol 2001;96:348-352Bravo L et al. Am K Gastroenterol 1999; 94: 2380-83

14-52%

15-36%

PPI44-55%

15-25%

Bis5-18%

5%

H2BUBT

HpSA

False negative rates

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Slide 29

How soon?

• As early as one day

When returns to positivity?

• Reliably after 2 weeks off PPI

• Ranitidine may have tolerance effect

Who’s on a PPI?

Points to consider when using tests of active infection

Gatta l. Am J Gastro 2004;99:823/ Patterson B et al. J Am Med Dir Assoc 2013; 13:429-32Ajumobi A et al. J Manag Care Pharm 2012;18:63-7 / De Souto Barreto P et al. J Am Med Dir Assoc 2013;14:265-9Rotman S et al. PLoS One 2013;8:e56060 / Reimer C et al. Aliment Pharmacol Ther 2009;30:725-372Mana F et al. Dig Liver Dis 2005;37:28-32

4.0% (2002) 9.2% (2009) 23.4% 37.8% 79.7%

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Slide 30 Case FG


– negative


adenocarcinoma



No H. pylori?...Patient FG was on PPI!

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Watch out for false negatives



Meds Blood Mucosa

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Slide 32 Acute GI bleeding

• Meta-analysis of 23 studies

• Mean prevalence 63-80%

• Multiple diagnostic modalities assessed

• Gold standard for diagnosis based on at least one independent diagnostic method

Gisbert JP et al. Am J Gastroenterol 2006; 101:848-863

Severe limitation: significant heterogeneity

•0.67

RUT

•0.70

Histo

•0.93

UBT

•0.87

HpSA

high prevalence setting raise index of suspicion

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Slide 33 Watch out for false negatives



Meds Blood Mucosa

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• Gastritis and chronic inflammation were severe when H. pylori existed in the gastric mucosa, as expected

• In contrast, the degree of atrophic gastritis and IM was more severe in seropositiveonly group compared to other two groups (seropositivity + histology positive, and seronegative)

• Suggest that the progression of atrophic gastritis and intestinal metaplasia seems to drive H. pylori out of the gastric mucosa

Kang HY et al. Dig Dis Sci 2006; 51:2310-2315Gisbert JP et al. Am J Gastroenterol 2006; 101:848-863

H. pylori IgG positivity with negative invasive tests represents past infection rather than false negative

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Slide 35 Case FG


– negative


adenocarcinoma



No H. pylori?...Did this confound results in patient FG?

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Slide 36 Non-invasive testing

Breath urea


• Sens 88-95%/spec 95-100%

• False positives rare

• False negatives

• acid suppressant therapy (40%)

• bismuth (55%)

• antibiotics

Stool Ag

• Detects HP via enzyme immunoassay

• Sens 94%/spec 86-92%

• False positive in UGIB -cross-reactivity with blood

• False negative

• ppi and bismuth (not h2b)

Serology

• Elisa to detect IgG

• Sens 90-100%

• Spec 76-96%

• Prevalence affects ppv

• If <20% (+) HP active infection ~50% of the time

Gatta l. Am J Gastro 2004;99:823Malfertheiner P et al. Gut 2007;56:772Chey WD et al. Am J Gastroenterol 2007;102:1808

Useful: •High pretest probability (ulcer), •May treat based on positive serology•Confirm negative serology

Useful: •Low pretest probability (young dyspepsia, low prevalence area)•Negative useful to exclude infection •Confirm positive serology

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Case FG


– Negative

• H. Pylori Serology


adenocarcinoma



No H. pylori?...POSITIVE

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Slide 38 The downsides?

• 6-12 months to clear Ab

• Ask the patient!Not active infection

• Economic model: 50 yo Japanese Americans, screening with HP serology was more cost effective than mammography

Not cost effective

• C. diff, rare, case report

• Not usually w. standard HP RxAbx

complications

• Most significant issues with 3rd gen cephalosporins, FQ, Abx for S. aureus, carbapenems

Abx resistanceDeshpande et al. Practice Based Pharmacology 2013WHO fact sheet 2014; No 194Parsonnet et al. Lancet 1996;348:150

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Slide 39 H. pylori antibody is FOREVER

• Titers decline by approximately 50% at 3 months

• 60% have undetectable titers at 18 months

• After therapy, seroconversion from detectable to undetectable levels have specificity of 100% for detecting the eradication

Feldman M et al. JAMA 1998; 280:363Lerang F et al. Scan J Gastroenterol 1998; 33:710-5

Biopsy proven infection

Undetectable IgG65%

Detectable IgG35%

Bx proven cure Persistent gastritis

Useful >1 yr post tx eradication

18 mo

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The prevalence of disease is low

The question: what is the prevalence among patients in Chicago

http://en.wikipedia.org/wiki/Demographics_of_Chicagohttp://www.radicalcartography.net/index.html?chicagodotsen.wikipedia.org/wiki/File:African_American_Population_by_Census_Tract_in_Chicago,_IL_(2011).svg

caucasian32%

hispanic29%

asian5.5%

americanindian0.5%

african american

33%

Eastern Europe?Poles and Serbians in Chicago are their largest ethnic communities outside of Poland and Serbia

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Slide 41

http://quickfacts.census.gov/qfd/states/17/1714000.html

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Slide 42

Cauasian

• 34%

• 26%

• 26%

African American

• 70%

• 66%

• 53%

Hispanic

• 65%

• 62%

Prevalence of H. pylori

Graham D et al. Gastroenterology 1991;100:1495-501Malaty H et al. Gastroenterology 1992;103:813-6Everhart J et al. J Infect Dis 2000;181:1359-63

N=485, Houston

n=7465, Nhanes

N=108, Houston

based on serology

• asymptomatic patients

• adjusted for age, income, education, other clinical factors

Sero-positivity significantly higher in African American and Hispanic population

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Prevalence of H. pylori

Cauasian

• 24%

• 15%

African American

• 28%

• 29%

Hispanic

• 40%

• 36%

Smith J et al Conn Med 2009;713:133-7Portocarrero D et al. J Clin Gastroenterol 2012;46:431-2

n=253assymptomatic

N=248 egdssymptomatic

based on histology

Clinical symptoms were not associated with HP positivity (but ethnicity was)

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Slide 44 The prevalence is decreasing

Cauasian

• 34%

• 26%

• 26%

• 21%

African American

• 70%

• 66%

• 53%

• 52%

Hispanic

• 65%

• 62%

• 64%

Graham D et al. Gastroenterology 1991;100:1495-501Malaty H et al. Gastroenterology 1992;103:813-6Everhart J et al. J Infect Dis 2000;181:1359-63

• 2012 update

• Overall seroprevalence decreased from 33% to 31%

n=7465, Nhanes

N=485, Houston

N=108, Houston

2012 update

decline in HP seroprevalence affects primarily the Caucasian population

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Slide 45

Everhart J et al. J Infect Dis 2000;181:1359-63Grad Y et al. Am J Epidemiol 2012;175:54-9

Hispanic African American

CaucasianOverall

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Does treatment reduce risk of gastric cancer ?

Fuccio L et al. Ann Intern Med 2009;151:121Ma JL et al. J Natl Cancer Inst 2012;104:488Lee YC et al. Gut 2013;62:676

• Meta-analysis 2009 – 7 trials

• significantly lower rate of gastric cancer in patients randomized to eradication

• 1.1 vs. 1.7% (RR 0.65,95% CI 0.43-0.98)

High incidence areas

(China, Japan, Columbia)

• Placebo controlled trial, n=3365; 14.7 yr f/u

• significant reduction in gastric cancer incidence in patients who underwent eradication

• 3.0% vs. 4.6 %(OR 0.61,95% CI 0.38-0.96)

China, 15 year follow up

• Mass eradication study over 5 years

• There was decrease in pud and gastric cancer

Taiwan, 5 year follow up

Eradication seem to reduce the risk of gastric cancer in “high risk” patients

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Slide 47




topographic mapping




ASGE Guidelines

•Who is considered higher than “average risk”?

•What could be done before “dysplasia?” at the point of “intestinal metaplasia”

•How and who should be tested for H. pylori?


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Slide 48 Gastric Intestinal Metaplasia?

• Adaptive response to environmental stimuli such as HP infection, smoking, high salt intake

• Gastric mucosa is replaced by mucosa that resembles intestinal epithelium

• Morphologically characterized by mucus secreting goblet cells

• Typically assymptomatic

• My be associated with achlorhydria sibo and bloating, flatulence, abdominal discomfort, and diarrhea

• High association of IM with gastric cancer

Leung WK et al. Aliment Pharmacol Ther 2002;16:1209-1216Filipe MI et al. Int J Cancer 1994;57:324-329Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201

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Filipe MI et al. Int J Cancer 1994;57:324-329Uemura N et al. N Engl J Med 2001;345:784-9You WC et al. Int J Cancer 1999;83:615-619

Slovenia: •Patients with IM have a >10 fold increased risk of developing gastric cancer

Japan: •IM conferred a 6.4x higher risk of developing gastric cancer

China: OR for gastric cancer ranged from 17.1 to 29.3

Increased risk of gastric cancer are from varying populations (not just Asia)

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Slide 50

RATIONALE FOR/AGAINST SURVEILLANCE?

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Slide 51 Against surveillance

• Developed countries: low prevalence, low yield, high cost

• Gastric IM is difficult to recognize endoscopically (unlike premalignant lesions of esophagus and colon)

• Findings at conventional endoscopy often still correlate poorly with histology diagnoses

• Differences in training and approach from Western vs. Asian countries (especially Japan), where lesions are frequently established on endscopy vs. histologic evaluation of random biopsies

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Endoscopic findings may be subtle

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Slide 53

Which is intestinal metaplasia?

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Slide 54

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Pro screening/ surveillance

• Many compelling reasons

Leung WK et al. Aliment Pharmacol Ther 2002;16:1209-1216

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Slide 56

• Aim: investigate whether the eradication of HP reduces risk of developing gastric cancer

• Nippon Fukuyama Hospital outpatient clinic, 1995-2003

• n=1342 consecutive patients with PUD and who had received HP eradication

Take S. et al. Am J Gastroenterol 2005;100:1037-1042

Compelling reason # 1 –ERADICATION WORKS

Index endoscopyn=1342

•Gastric atrophy classified by histology. •IM diagnosed endoscopically as absent/present•HP infection = positive bacterial culture from endoscopic biopsy and urease test

evaluate ulcers, background gastric mucosa, HP infection

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Slide 57 Methods




495 du776 gu

1995-99: 619pts, 2 wk dual therapy (amox 750 bid/ppi bid)1997-03: 670 pts, 1wk triple tx(amox 750 bid/clarith 200mg or 400mg bid)1995-03: 53 pts, 1wk metronidazole 500 bid, amox 750 bid, or clarithro200mg bid and ppi bid

Confirm eradication

•1-2 months after tx•Breath test and f/u endoscopy performed to determine HP status

•treatment

n=1120 completed >/= 1 year

•endoscopy and urea breath tests yearly

•followed for up 8.6 years (mean 3.4y)

HP cured when bacterial culture, urease test, and urea breath test all negative

71 both

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Methods




495 du776 gu 71 both

Confirm eradication

n=1120 completed >/= 1 year

n=944 cured of infection

n=176 persistent infection

n=8Gastric cancer

n=4Gastric cancer

All gastric cancer in patients with GU, none in DU (p=0.005)

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Slide 59


•Risk of developing gastric cancer in patients cured of infection vs. persistent infection was significantly lower•1.21% vs. 3.80% at 5 yrs (p=0.04) – patients with PUD•2.00% vs. 6.41% at 5 yrs (p=0.04 ) – patients with GU

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Slide 60


•persistent infection was the most significant risk factor for gastric ca •H. pylori eradication may reduce risk of gastric cancer

Is eradication enough?

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• Aim:

(1) identify risk factors for progression of gastric IM

(2) identify high risk subgroup that might warrant intensive surveillance

• University of China Hong Kong

• Volunteers residing in Yantai county of Shandong invited for screening endoscopy

• Randomized control study over 5 years.

• HP(+) patients received either anti-HP therapy or placebo

Leung WK et al. Gut 2004;53:1244-1249

Compelling reason # 2 –ERADICATION IS NOT ENOUGH

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Slide 62

n= 587 HP (+)

n=220 n=215

n=292placebo

n=2951 week tx

152 LTFU

f/u endoscopy 5 year analysis

n=164 (74.5%)

n=20 (9.3%)

n=6 cancers10 (2.3%) developed invasive gastric ca during f/u

n=4 cancers

HP clearanceconfirmed by histology

Leung WK et al. Gut 2004;53:1244-1249

Index endoscopy

H. pylori infection= both rapid urease and histology positive

All completed the 2 endoscopies or found gastric cancer within the 5 year f/u

Progression of IM = higher score at five years compared with baseline

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Slide 63 Results

• Eradication of HP infection significantly retards but does not eliminate IM progression

• 52.9% had progression of IM over 5 years

Leung WK et al. Gut 2004;53:1244-1249

Conclusions:•Identified a subgroup (age + persistent HPI) at high risk of progression that may warrant more intensive endoscopic surveillance

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Example of Japan

Compelling reason # 3 –EVIDENCE OF UTILITY

Oshima A et al. Int J Cancer 1986:38:829-833Hisamichi S et al. Cancer Detec Prev 1988:11:323-329Lee, KJ et al. Int J Cancer 2006:118;2315-2321

1986: Case control study in farm village, Osaka - screening since 1962•OR of death from stomach cancer in screened vs. unscreened was 0.519 males / OR 0.486 females•Effective in reducing stomach cancer mortality by half

•1988: prospective cohort study•incidence rate same•RR diagnosing advanced stomach cancer 0.4-0.7 •Effective in reducing mortality from stomach cancer

• Prospective study over 13 year f/u in Japan involving 42150 patients

• 2 fold decrease in mortality in screened vs. unscreened patients (RR=0.52;95%CI 0.36-0.74)

• Significant decrease in incidence of advanced gastric cancer in screened subjects (RR = 0.75;95% CI=0.58-0.96)

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Slide 65

• Aim: to determine the incidence of gastric cancers in this “high risk” (IM, ulcers, polyps) group and to evaluate the potential for early diagnosis and treatment

• Dyspepsia clinics in area of the Queen Elizabeth and SandwellDistrict General Hospital, 1984-1988

• Patients over age 40 referred to dyspepsia clinic

Whiting JL et al. Gut 2002;50:378-381

Compelling reason # 4 –EVIDENCE OF UTILITY EXTENDS BEYOND ASIA

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Slide 66 Methods

n=14 cancers (8.4%)

n=166 accepted

n=368 (21%) lesions requiring f/u

n=22 (1.3%) gastric cancer

n=1753 OAE

•offered surveillance endoscopy

Requiring followup:•dysplasia, IM, AG, foveolarhyperplasia, regenerative changes, polyps, ulcers

•annual endoscopy•ulcers re-examined q2mo until healing


•10 years follow-up

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Results

• More cancers detected from surveillance were of an earlier stage than those detected at open access

• 5year survival was significantly higher than tumors detected at open access

*

stage I /II67% vs. 23%;

p<0.05

50% vs. 10%; p=0.006


Conclude:•In patients with IM, annual surveillance can detect most new tumors at early stage with major improvement in survival

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Slide 68

United states 5.8

Globocan 2008: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5 version 2.0, IARC Press 2008Take S. et al. Am J Gastroenterol 2005;100:1037-1042

Compelling reason # 5 – PERSPECTIVE ON THE BURDEN OF DISEASE

For example:We screen for Barretts and then do surveillance for esophageal cancer

(gastric cancer 5.7)

Esophageal vs. gastric cancer•Burden of disease

Esophageal vs. gastric cancer•Incidence of disease after detection of premalignant lesions

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Slide 69 we

Hvid-Jensen et al. N Engl J Med 2011;365:1378-83Uemura N et al. N Engl J Med 2001;345:784-9Leung WK et al. Gut 2004;53:1244-1249

BE is a strong risk factor for esophageal

adenocarcinoma

Annual risk = 0.12%

(lower than assumed 0.5%)

Risk is increased to 0.26% when high grade dysplasia included

HP(+) is a strong risk factor for gastric adenocarcinoma

Annual risk = is 0.37%

Risk is 0.5%/year HP (+) 0.24%/yr HP eradication

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topographic mapping




ASGE Guidelines

•Who is considered higher than “average risk”?

•What could be done before “dysplasia?” at the point of “intestinal metaplasia”

•How and who should be tested for H. pylori?


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Slide 71 Proposed Strategy for Screening and Surveillancefor low prevalence regions

de Vries AC et al. Helicobacter2007;12:1-15

Epidemiologic Risk Factors

Serologic Screening

Histologic Evaluation

Endoscopic Surveillance

Inva

sive

nes

s

Gas

tric

can

cer

risk

Identify population for noninvasive screening

Identify premalignant lesions at risk of progression

HP eradication

?

Early tx dysplasia

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Slide 72

No surveillanceIndividualize :surveillance EGD

Repeat EGD mapping in 3 yrs

High risk patient?Surveillance EGD mapping q2-3yrs

NoUnknownYes

Extensive or incomplete IM

Assess HP, treat if (+)

Intestinal metaplasia

High risk patient?

yes yesno no

Individualize :repeat EGD mapping

High risk patient:•Family history gastric ca•Noncaucasian: african american, hispanic, asian•Immigrant : east asia or mountainous latin america Correa P. et al. Am J Gastro 2010;105:493

Dinis-ribeiro M. et al. Endoscopy 2012;44:74-94

MANAGEMENT ALGORITHM

•If biopsies negative for HP noninvasive testing

Characterize:•histologic subtype (complete vs incomplete) •extent (limited vs. extensive) •determine the risk of malignancy and guide surveillance

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The discrepancy…

The United states is a

diverse placeWe do not

individualize risk factors

IM is a premalignant

state We do not offer surveillance

H. pylori is a carcinogen We do not

screen for it

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Slide 74 How do we change?

Identify Test

Treat Eradicate

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Slide 75 How do we change?

Family history gastric cancer

Refractory

H. pylori infection

Refractory gastric ulcers

Abnormal gastric

histology: •Intestinal metaplasia•Atrophic gastritis•Autoimmune gastritis•Hyperplasia/hyperplastic polyps•Adenomatous polyps•Regenerative changes•Carcinoids

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How do we change?

Kn

ow

n

Benefit

Un

kno

wn Low

prevalence places

Un

kno

wn High risk

populations amongst low prevalence places

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Slide 77 Take Home Points

• Patients at risk for developing gastric cancer can be identified by ethnicity, country of origin, HP status

• HP screening and eradication may reduce the risk of gastric cancer

• Surveillance of high risk lesions may increase detection of early stage gastric cancer and therefore reduce mortality

• Given inherent diversity of the US, there may not be a true “average” risk patient risk assessment needs to be individualized

• There is a role for targeted screening and surveillance for gastric cancer amongst “high risk populations” within a traditionally “low risk region”

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Slide 78

THANK YOU!Questions?

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