Slide 1 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 Slide 2 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 Case FG Exam unremarkable Labs: Hb 7.4, microcytic Slide 3 Endoscopy
Slide 4 How could this happen Slide 5 Screening and surveillance for the early detection of GASTRIC CANCER Slide 6 Background Gastric cancer 4 th most common cancer in the world 937,00 new cases per year, accounting for nearly 10% of all new cancers 2 nd 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;24:193-201 de Vries AC et al. Helicobacter2007;12:1-15 devries AC and Kuipers EJ. Helicobacter 2007;12:22-31
Slide 7 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 Slide 8 Burden of Disease High incidence East Asia In the west, though incidence is Central America low, mortality remains high because South America index of suspicion is low Netherlands Late diagnosis 5 yr survival <20% 8.6 Early detection 5 yr survival as high as 90% China China 41.3 50 US 5.7 Japan Japan 46.8 93 Sudan 2.5 Of note, it is not clearly associated with the developing Globocan 2008: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5 version 2.0, IARC Press 2008 world eg: Africa Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201 de Vries AC et al. Helicobacter2007;12:1-15 Slide 9 UNANSWERED ASGE Guidelines QUESTIONS Benefits of surveillance has been evaluated and known How H. pylori and should who be should treated be if tested found for H. pylori? What If low grade could dysplasia be done is before detected, dysplasia? surveillance EGD with topographic at the point mapping of intestinal metaplasia Who For US, is the considered progression higher of IM than to cancer average is low and risk? 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
Slide 10 RISK FACTORS FOR GASTRIC CANCER Slide 11 Risk Factors Habitat H. pylori Host Smoking Nitrate high diet Low fresh fruit and vegetables Alcohol use low socioeconomic class blood group A familial occurrence of gastric cancer H. pylori virulence Host genetics Interaction Slide 12 H. pylori discovered 1980s 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) 1994 human carcinogen We don t Cigarette smoking screen HPV H. Pylori HCV The most successful human pathogen ~50% human population infected Screen for class 1 carcinogens Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201 devries AC and Kuipers EJ. Helicobacter 2007;12:22-31 Malfertheiner P et al. Gut 1012; 61:646-664
Slide 13 Complicated interrelationship genetic bacterial environs non-neoplastic malignancy Majority of the course is benign Slide 14 Issue of geography East vs. West Japan Western Europe HP 60% HP 40% (+) (-) (+) (-) AG: 80% AG: 10% AG: to 60% AG: 5-10% IM: 40-50% IM: 40% IM: 5% IM: 5-10% The pattern to notice: When HP (+) higher incidence of AG or IM regardless of world region de Vries AC et al. Helicobacter2007;12:1-15 Slide 15 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 Gut 2001;49:347-353 Kim N et al. J Clin Gastroenterol 2008;42:448-454 Rokkas T et al. Helicobacter 2007;12:32-38
Slide 16 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 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 Slide 18 New recommendations Population based screening for high risk groups Asian pacific guidelines European guidelines ACG guidelines Population based screening for high risk groups Describe high risk populations but consider strategies for screening such groups as controversial WHO to screen 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;103:510 Malfertheiner P et al. Management of Helicobacter pylori infection the Maastricht IV/Florence Consensus Report. Gt 2012;61:646 Chey WD et al. Practice Parameters Committee of the ACG. ACG guideline on the management of Heliocbacter pylori infection. AJG 2007;102:1808
Slide 19 Case FG Urea breath test: negative Endoscopy: No H. pylori?... Pathology: Mass: invasive adenocarcinoma Random: atrophic gastritis and multiple foci of intestinal metaplasia involving the antrum and corpus of the stomach H. pylori negative Slide 20 Choosing the right test HOW to screen Pretest Clinical setting probability Sensitivity and specificity Cost effectiveness and availability Gatta l. Am J Gastro 2004;99:823 Slide 21 Endoscopic testing Rapid Urease Test Histology Culture Hydrolysis of urea Sens 90-95% Spec 95-100% Sens >95% Spec >95% Limited by cost, not usually needed Only for sensitivity in refractory disease Chey W et al. Am J Gastroenterol 2007;102:1808-1825
Slide 22 Non-invasive testing Breath urea Stool Ag Serology Hydrolysis of urea Sens 88-95% Spec 95-100% False negatives Detects HP via enzyme immunoassay Sens 94% Spec 86-92% Recommended as test of choice Most accurate noninvasive test for active HPI Gatta l. Am J Gastro 2004;99:823 Malfertheiner P et al. Gut 1012; 61:646-664 Slide 23 Watch out for false negatives Meds Blood Mucosa Decreased sensitivity Gatta l. Am J Gastro 2004;99:823 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 Gatta l. Am J Gastro 2004;99:823
Slide 25 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 Gatta l. Am J Gastro 2004;99:823 Slide 26 n=152 eligible n=72 enrolled n=24 omeprazole 20/d n=24 esomeprazole 40mg/d n=24 AlOH 800mg/d UBT HpSA UBT HpSA UBT HpSA 2 weeks treatment 2 weeks treatment 2 weeks treatment UBT Stool Test UBT Stool Test UBT Stool Test Gatta l. Am J Gastro 2004;99:823 Slide 27 Results Sensitivity: UBT Stool Test PPI Antacid PPI Antacid Baseline After treatment 72.9-85.4% 100% 100% 97.8% 90.0% 100% 83.0% 90.0% Conclusion: PPI decreases sensitivity of UBT and HpSA Antacid will not alter sensitivity of UBT or HpSA Gatta l. Am J Gastro 2004;99:823
Slide 28 And Ranitidine or Bismuth? False negative rates PPI UBT 14-52% HpSA 15-36% Bis 44-55% 15-25% H2B 5-18% 5% Gatta l. Am J Gastro 2004;99:823 Laine L et al. 1998 / Manes G et al. 2001 / Bravo L et al. 1999 Parente F et al / Connor S et al 1999 / Dulbecco P et al. 2003 / Savarino V et al. 2000 Savarino V et al. Am J Gastroenterol 2001;96:348-352 Bravo L et al. Am K Gastroenterol 1999; 94: 2380-83 Slide 29 Points to consider when using tests of active infection 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? 4.0% (2002) 9.2% (2009) 23.4% 37.8% 79.7% Gatta l. Am J Gastro 2004;99:823/ Patterson B et al. J Am Med Dir Assoc 2013; 13:429-32 Ajumobi A et al. J Manag Care Pharm 2012;18:63-7 / De Souto Barreto P et al. J Am Med Dir Assoc 2013;14:265-9 Rotman S et al. PLoS One 2013;8:e56060 / Reimer C et al. Aliment Pharmacol Ther 2009;30:725-372 Mana F et al. Dig Liver Dis 2005;37:28-32 Slide 30 Case FG Urea breath test: negative Endoscopy: Patient No H. pylori?... FG was on PPI! Pathology: Mass: invasive adenocarcinoma Random: atrophic gastritis and multiple foci of intestinal metaplasia involving the antrum and corpus of the stomach H. pylori negative
Slide 31 Watch out for false negatives Meds Blood Mucosa Decreased sensitivity Gatta l. Am J Gastro 2004;99:823 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 0.67 RUT Severe limitation: significant heterogeneity 0.70 Histo 0.93 UBT 0.87 HpSA high prevalence setting raise index of suspicion Gisbert JP et al. Am J Gastroenterol 2006; 101:848-863 Slide 33 Watch out for false negatives Meds Blood Mucosa Decreased sensitivity Gatta l. Am J Gastro 2004;99:823
Slide 34 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 seropositive only 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 H. pylori IgG positivity with negative invasive tests represents past infection rather than false negative Kang HY et al. Dig Dis Sci 2006; 51:2310-2315 Gisbert JP et al. Am J Gastroenterol 2006; 101:848-863 Slide 35 Case FG Urea breath test: negative Endoscopy: Did this confound No H. pylori?... results in patient FG? Pathology: Mass: invasive adenocarcinoma Random: atrophic gastritis and multiple foci of intestinal metaplasia involving the antrum and corpus of the stomach H. pylori negative Slide 36 Non-invasive testing Breath urea Stool Ag Serology Hydrolysis of urea Detects HP via enzyme Sens 88-95%/spec Useful: 95- immunoassay 100% High pretest probability Sens 94%/spec (ulcer), 86-92% False positives rare False in UGIB - May treat based on positive serology False negatives cross-reactivity with Confirm negative serology acid suppressant blood therapy (40%) False negative bismuth Useful: (55%) ppi and bismuth (not antibiotics Low pretest probability h2b) (young dyspepsia, low prevalence area) Negative useful to exclude infection Confirm positive 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;99:823 Malfertheiner P et al. Gut 2007;56:772 Chey WD et al. Am J Gastroenterol 2007;102:1808
Slide 37 Urea breath test: Negative Case FG Endoscopy: H. Pylori Serology No POSITIVE H. pylori?... Pathology: Mass: invasive adenocarcinoma Random: atrophic gastritis and multiple foci of intestinal metaplasia involving the antrum and corpus of the stomach H. pylori negative Slide 38 The downsides? Not active infection Not cost effective Abx complications Abx resistance 6-12 months to clear Ab Ask the patient! Economic model: 50 yo Japanese Americans, screening with HP serology was more cost effective than mammography C. diff, rare, case report Not usually w. standard HP Rx Most significant issues with 3 rd gen cephalosporins, FQ, Abx for S. aureus, carbapenems Deshpande et al. Practice Based Pharmacology 2013 WHO fact sheet 2014; No 194 Parsonnet et al. Lancet 1996;348:150 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 Biopsy proven infection 18 moundetectable IgG Detectable IgG 65% 35% Bx proven cure Persistent gastritis Useful >1 yr post tx eradication Feldman M et al. JAMA 1998; 280:363 Lerang F et al. Scan J Gastroenterol 1998; 33:710-5
Slide 40 The prevalence of disease is low The question: what is the prevalence among patients in Chicago african american caucasian 33% 32% american indian hispanic asian 0.5% 29% 5.5% Eastern Europe? Poles and Serbians in Chicago are their largest ethnic communities outside of Poland and Serbia http://en.wikipedia.org/wiki/demographics_of_chicago http://www.radicalcartography.net/index.html?chicagodots en.wikipedia.org/wiki/file:african_american_population_by_census_tract_in_chicago,_il_(2011).svg Slide 41 http://quickfacts.census.gov/qfd/states/17/1714000.html Slide 42 based on serology 34% 26% 26% Cauasian Prevalence of H. pylori asymptomatic patients adjusted for age, income, education, other clinical factors African American 70% 66% 53% Sero-positivity significantly higher in African American and Hispanic population Hispanic N=485, Houston 65% N=108, Houston 62% n=7465, Nhanes Graham D et al. Gastroenterology 1991;100:1495-501 Malaty H et al. Gastroenterology 1992;103:813-6 Everhart J et al. J Infect Dis 2000;181:1359-63
Slide 43 based on histology 24% 15% Cauasian Prevalence of H. pylori African American 28% 29% Clinical symptoms were not associated with HP positivity (but ethnicity was) 40% 36% Hispanic N=248 egds symptomatic n=253 assymptomatic Smith J et al Conn Med 2009;713:133-7 Portocarrero D et al. J Clin Gastroenterol 2012;46:431-2 Slide 44 34% 26% 26% 21% The prevalence is decreasing 2012 update Overall seroprevalence decreased from 33% to 31% Cauasian African American 70% 66% 53% 52% decline in HP seroprevalence affects primarily the Caucasian population Hispanic N=485, Houston 65% N=108, Houston 62% n=7465, Nhanes 64% 2012 update Graham D et al. Gastroenterology 1991;100:1495-501 Malaty H et al. Gastroenterology 1992;103:813-6 Everhart J et al. J Infect Dis 2000;181:1359-63 Slide 45 Overall Caucasian African American Hispanic Everhart J et al. J Infect Dis 2000;181:1359-63 Grad Y et al. Am J Epidemiol 2012;175:54-9
Slide 46 Does treatment reduce risk of gastric cancer? High incidence areas (China, Japan, Columbia) 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) China, 15 year follow up 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) Taiwan, 5 year follow up Eradication seem to reduce the risk of gastric cancer in high risk patients Mass eradication study over 5 years There was decrease in pud and gastric cancer Fuccio L et al. Ann Intern Med 2009;151:121 Ma JL et al. J Natl Cancer Inst 2012;104:488 Lee YC et al. Gut 2013;62:676 Slide 47 UNANSWERED ASGE Guidelines QUESTIONS Benefits of surveillance has been evaluated and known How H. pylori and should who be should treated be if found tested for H. pylori? What If low grade could dysplasia be done is detected, before dysplasia? surveillance EGD with topographic at the point mapping of intestinal metaplasia Who For US, is the considered progression higher of IM to than cancer average is low and risk? 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 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;16:1209-1216 Filipe MI et al. Int J Cancer 1994;57:324-329 Busuttil RA and Boussioutas A. J Gastoenterol and Hepatology 2000;24:193-201
Slide 49 Japan: IM conferred a 6.4x higher risk of developing gastric cancer Slovenia: Patients with IM have a >10 fold increased risk of developing gastric cancer Increased risk of gastric cancer are from varying populations (not just Asia) China: OR for gastric cancer ranged from 17.1 to 29.3 Filipe MI et al. Int J Cancer 1994;57:324-329 Uemura N et al. N Engl J Med 2001;345:784-9 You WC et al. Int J Cancer 1999;83:615-619 Slide 50 RATIONALE FOR/AGAINST SURVEILLANCE? 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
Slide 52 Endoscopic findings may be subtle Slide 53 Which is intestinal metaplasia? Slide 54
Slide 55 Pro screening/ surveillance Many compelling reasons Leung WK et al. Aliment Pharmacol Ther 2002;16:1209-1216 Slide 56 Compelling reason # 1 ERADICATION WORKS 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 Index endoscopy n=1342 evaluate ulcers, background gastric mucosa, HP infection Gastric atrophy classified by histology. IM diagnosed endoscopically as absent/present HP infection = positive bacterial culture from endoscopic biopsy and urease test Take S. et al. Am J Gastroenterol 2005;100:1037-1042 Slide 57 Methods evaluate ulcers, background gastric mucosa, HP infection 776 gu Index endoscopy n=1342 495 du 71 both treatment HP Confirm cured when eradication bacterial culture, urease test, and 1-2 months after tx urea breath test all negative Breath test and f/u endoscopy performed 1995-99: 619pts, 2 wk dual therapy to determine HP status (amox 750 bid/ppi bid) 1997-03: 670 pts, 1wk triple tx n=1120 endoscopy and urea (amox 750 bid/clarith 200mg or completed >/= 1 year breath tests yearly 400mg bid) 1995-03: 53 pts, 1wk metronidazole 500 bid, amox 750 bid, or clarithro followed for up 8.6 200mg bid and ppi bid years (mean 3.4y) Take S. et al. Am J Gastroenterol 2005;100:1037-1042
Slide 58 evaluate ulcers, background gastric mucosa, HP infection All gastric cancer in patients with GU, none in DU (p=0.005) Methods Index endoscopy n=1342 776 gu 495 du 71 both Confirm eradication n=1120 completed >/= 1 year n=176 persistent infection n=4 Gastric cancer n=944 cured of infection n=8 Gastric cancer Take S. et al. Am J Gastroenterol 2005;100:1037-1042 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 Take S. et al. Am J Gastroenterol 2005;100:1037-1042 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? Take S. et al. Am J Gastroenterol 2005;100:1037-1042
Slide 61 Compelling reason # 2 ERADICATION IS NOT ENOUGH 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 Slide 62 n=295 1 week tx n= 587 HP (+) Index endoscopy n=292 placebo 152 LTFU n=220 f/u endoscopy n=215 5 year analysis n=164 HP clearance n=20 (74.5%) confirmed by histology (9.3%) All completed the 2 endoscopies or found gastric cancer within the 5 year f/u n=4 cancers H. pylori infection= both rapid urease and histology positive 10 (2.3%) developed n=6 cancers invasive gastric ca during f/u Progression of IM = higher score at five years compared with baseline Leung WK et al. Gut 2004;53:1244-1249 Slide 63 Results Eradication of HP infection significantly retards but does not eliminate IM progression 52.9% had progression of IM over 5 years Conclusions: Identified a subgroup (age + persistent HPI) at high risk of progression that may warrant more intensive endoscopic surveillance Leung WK et al. Gut 2004;53:1244-1249
Slide 64 Compelling reason # 3 EVIDENCE OF UTILITY Example of Japan 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) Oshima A et al. Int J Cancer 1986:38:829-833 Hisamichi S et al. Cancer Detec Prev 1988:11:323-329 Lee, KJ et al. Int J Cancer 2006:118;2315-2321 Slide 65 Compelling reason # 4 EVIDENCE OF UTILITY EXTENDS BEYOND ASIA 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 Sandwell District General Hospital, 1984-1988 Patients over age 40 referred to dyspepsia clinic Whiting JL et al. Gut 2002;50:378-381 Slide 66 Methods n=1753 OAE n=22 (1.3%) gastric cancer Requiring followup: dysplasia, IM, AG, foveolar hyperplasia, regenerative changes, polyps, ulcers n=368 (21%) offered surveillance lesions requiring f/u endoscopy n=166 annual endoscopy accepted ulcers re-examined q2mo until healing n=14 cancers (8.4%) 10 years follow-up Whiting JL et al. Gut 2002;50:378-381
Slide 67 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 /II 67% 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 Whiting JL et al. Gut 2002;50:378-381 Slide 68 Compelling reason # 5 PERSPECTIVE ON THE BURDEN OF DISEASE For example: We screen for Barretts and then do surveillance for esophageal cancer United states 5.8 (gastric cancer 5.7) Esophageal vs. gastric cancer Burden of disease Esophageal vs. gastric cancer Incidence of disease after detection of premalignant lesions Globocan 2008: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5 version 2.0, IARC Press 2008 Take S. et al. Am J Gastroenterol 2005;100:1037-1042 Slide 69 we BE is a strong risk factor for esophageal adenocarcinoma Annual risk = 0.12% (lower than assumed 0.5%) HP(+) is a strong risk factor for gastric adenocarcinoma Annual risk = is 0.37% Risk is increased to 0.26% when high grade dysplasia included Risk is 0.5%/year HP (+) 0.24%/yr HP eradication Hvid-Jensen et al. N Engl J Med 2011;365:1378-83 Uemura N et al. N Engl J Med 2001;345:784-9 Leung WK et al. Gut 2004;53:1244-1249
Invasiveness Gastric cancer risk Slide 70 UNANSWERED ASGE Guidelines QUESTIONS Benefits of surveillance has been evaluated and known How H. pylori and should who be should treated be if found tested for H. pylori? What If low grade could dysplasia be done is detected, before dysplasia? surveillance EGD with topographic at the point mapping of intestinal metaplasia Who For US, is the considered progression higher of IM to than cancer average is low and risk? 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 Slide 71 Proposed Strategy for Screening and Surveillance for low prevalence regions Epidemiologic Risk Factors Identify population for noninvasive screening Serologic Screening Histologic Evaluation Endoscopic Surveillance HP eradication? Identify premalignant lesions at risk of progression Early tx dysplasia de Vries AC et al. Helicobacter2007;12:1-15 Slide 72 Intestinal metaplasia MANAGEMENT ALGORITHM Yes Assess HP, treat If if biopsies (+) negative for HP noninvasive testing Extensive or incomplete IM Unknown No Surveillance EGD High risk patient? High risk patient? mapping q2-3yrs yes no yes no Characterize: histologic subtype (complete Repeat vsegd incomplete) Individualize : extent (limited vs. extensive) mapping in 3 yrs repeat EGD mapping determine the risk of malignancy and guide surveillance High risk patient: Individualize : No surveillance Family history gastric ca surveillance EGD 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
Slide 73 The discrepancy H. pylori is a carcinogen We do not screen for it IM is a premalignant state We do not offer surveillance The United states is a diverse place We do not individualize risk factors Slide 74 How do we change? Identify Treat Test Eradicate Slide 75 How do we change? Family history gastric cancer Refractory gastric ulcers Refractory H. pylori infection Abnormal gastric histology: Intestinal metaplasia Atrophic gastritis Autoimmune gastritis Hyperplasia/hyperplastic polyps Adenomatous polyps Regenerative changes Carcinoids
Known Unknown Unknown Slide 76 How do we change? Benefit Low prevalence places High risk populations amongst low prevalence places 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 Slide 78 Questions? THANK YOU!