Dr. Shailja Shah is a gastroenterologist and clinical researcher at VA San Diego and the University of California, San Diego. Dr. Shah leads a multidisciplinary research program anchored in defining non-genetic, genetic, and systems-level determinants of H. pylori treatment- and disease-related clinical outcomes, including gastric cancer, among high-risk populations. She is also actively involved in research and public policy initiatives to promote gastric cancer prevention and early detection efforts. Dr. Shah’s current and prior sources of funding include the US Dept of Veterans Affairs, AHRQ, NIH, and the American Gastroenterological Association (AGA).

As a gastroenterologist and physician scientist at UCSD/VA San Diego and Moores Cancer Center, when you think about early detection and surveillance of gastric cancer, what are some of the signs and symptoms you look for and how would you factor in risk-based screenings?

Dr. Shah: In the United States, gastric cancer is overlooked because it is thought of as a rare cancer when, in fact, it's more common than esophageal cancer and in certain groups even approaches rates of colorectal cancer. This is important because we have clear guidelines on who to screen for esophageal and colorectal cancer, but we don't have these guidelines for gastric cancer.

The majority of gastric cancer cases in the United States is non-cardia gastric cancer, which refers to the location in the stomach that this type of cancer occurs. This is in comparison to gastric cancer of the cardia which makes up a much smaller percentage. I mention this up front because the risk factor profiles for these two cancers based on anatomic location are different. Cardia gastric cancer mostly tracks with risk factors for esophageal adenocarcinoma while non-cardia gastric cancer is more common in non-white groups who share a disproportionate burden—with some groups as much as 13.5-fold higher than non-Hispanic whites.

The key to the discussion of risk-based screening for non-cardia gastric cancer is that gastric cancer is typically asymptomatic or presents with only non-specific symptoms until it's in the more advanced stages. There's no cure for gastric cancer once it is in this advanced stage, which is really when symptoms prompt the diagnostic workup. When gastric cancer is caught in the early stage where it is asymptomatic or associated with non-specific symptoms that might not prompt an immediate diagnostic workup—this is the stage that resection would be curative.

There are countries such as Japan and South Korea where endoscopic screening for gastric cancer routinely occurs. This has translated into significant reductions in gastric cancer mortality, although notably has not substantially decreased the actual incidence of cancer. This again suggests that the benefit is early detection and the opportunity for curative resection—which can be accomplished either endoscopically or surgically. The United States population overall is not universally high risk for gastric cancer; however, there are certain identifiable high-risk groups who might benefit from endoscopy for early detection. These include non-white groups and immigrants from high risk countries for gastric cancer, people with a family history of gastric cancer, as well as people with gastric precancerous changes such as atrophic gastritis and intestinal metaplasia. These precancerous changes most often are the result of chronic H. pylori infection.

We don't have very precise risk stratification models, and this is a much-needed area of research. We do, however, have evidence from cost-effectiveness analyses that upper endoscopy for gastric cancer screening at the time of colonoscopy for colorectal cancer screening might be cost effective for non-white race and ethnic groups. At the very least, data from these modeling studies can form a starting point when we think of risk-based screening; ideally, we will have data from prospective studies to guide our approach to gastric cancer screening.

Since H. pylori is one of the strongest risk factors for non-cardia gastric cancer, what is your detailed approach to diagnosis and management?

Dr. Shah: H. pylori is a gram-negative bacterium and, globally, it is the most common chronic bacterial infection. Some studies estimate that over half the world's population is infected with H. pylori. It is difficult to get a precise estimate of the global burden of H. pylori, since many times this infection is asymptomatic and it is not one that is routinely screened for in most parts of the world, including the United States. Generally, testing for H. pylori is triggered by GI symptoms such as dyspepsia, abdominal discomfort, or in patients who don't have symptoms, the things that might trigger testing would be a family history of gastric cancer, unexplained iron deficiency, long term NSAID use, and a few other situations.

It is important to diagnose H. pylori because chronic untreated infection is associated with gastric inflammation, which in some cases can progress to loss of the normal gastric glands, a condition known as atrophic gastritis, and, if replaced by intestinal-type tissue, intestinal metaplasia. Such conditions are associated with significantly higher risk of gastric dysplasia and cancer, particularly if there is ongoing H. pylori infection. This stepwise cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric adenocarcinoma is known as the correa cascade, for which H. pylori is the most common trigger.

We know that H. pylori eradication with antibiotics and high dose acid suppression does improve that inflammation and reduces the risk of gastric cancer. But the key here is that the biggest benefit of H. pylori eradication is eradicating H. pylori prior to the development severe atrophic gastritis and intestinal metaplasia. Therefore, simply testing and treating for H. pylori is not enough for gastric cancer prevention since some people might already have these advanced changes, since these typically don't cause symptoms. This forms the basis for endoscopic surveillance of these precancerous conditions, which is detailed in the most recent AGA guidelines and clinical practice update on intestinal metaplasia and atrophic gastritis, respectively.

H. pylori eradication still a cornerstone of gastric cancer prevention and risk reduction. Careful treatment selection and ensuring that eradication is confirmed warrants emphasis, particularly in the face of rising rates of H. pylori eradication failure. My key takeaway points for H. pylori eradication therapy is that prior to prescribing treatment, it's very important to review patients prior antibiotic exposures specifically macrolides and fluoroquinolones, since patients who have had treatment with these antibiotics for any condition are more likely to be colonized with resistant H. pylori strains. Clarithromycin-triple therapy should not be used unless patients are confirmed to be colonized with clarithromycin susceptible H. pylori. Bismuth-based quadruple therapy is really the preferred first line treatment instead of clarithromycin-based triple therapy given the high rates of clarithromycin resistance. It's also important to provide patients with anticipatory guidance regarding both the importance of completing the full course, as well as some expected possible side effects of antibiotics such as GI upset, nausea. The other tenant therapy is ensuring appropriate gastric acid suppression, which is a point emphasized in the recently published AGA clinical practice update on H. pylori management. All patients should have repeat non-serological H. pylori testing to ensure that eradication was successful. To reduce false positive or false negative results, this repeat testing should be done at least 2-4 weeks after completion of therapy and with patients off PPI therapy for at least 1-2 weeks.

What have you found to be some of the key disparities in gastric cancer particularly as it pertains to the racial and ethnic groups in the United States?

Dr. Shah: Racial and ethnic differences in gastric cancer incidence is a defining factor for gastric cancer in the United States. Our team recently conducted a population-based analysis of the California Cancer Registry, which is one of, if not the largest and most diverse of the SEER cancer registries. The results of this study highlighted the disparity in risk of gastric cancer based on race/ethnicity. All non-white groups in the US had a significantly higher risk of non-cardia gastric cancer compared to non-Hispanic whites. This was particularly striking in the age group that we generally consider for cancer screening, where there was anywhere from 2-fold up to 13.5-fold higher risk of non-cardia gastric cancer compared to the reference non-Hispanic whites. In some of these groups for example, Korean American men above the age of 50, these rates were on par with colorectal cancer rates. Even more concerning, it is possible that these estimates are actually underestimating the true burden of disease, since early cancer is asymptomatic most of the time and might go undiagnosed in the absence of screening.

We also know that immigrants from countries where gastric cancer incidence is high, also retain that increased risk and mortality even when they immigrate to countries gastric cancer incidence is low overall. Admittedly, this risk varies depending on immigrant generation and level of acculturation, including dietary practices, and other factors. The risk is observed to decrease over subsequent generations and depending on acculturation, which underscores opportunities for research into interventions and initiatives to address modifiable risk factors.

Given that immigrants from countries of high gastric cancer, including Asian Americans and Hispanics, comprise the vast majority of population growth in the United States, the public health implications are enormous if we continue to be complacent on gastric cancer prevention and early detection efforts.

As the fifth most common cancer and the third most common cause of cancer related deaths, based on recent studies and your personal experiences as a medical practitioner, also considering the gastric cancer does not cause symptoms until it is in the advanced stage, what are your recommendations as it relates to early detection and improving gastric cancer related outcomes?

Dr. Shah: The first step in my opinion, is recognizing that gastric cancer disproportionately affects certain populations in the US like I mentioned, especially racial and ethnic minorities and other under-represented populations, including US veterans. As a VA clinician and a VA investigator, we see that risk factors for gastric cancer, including H. pylori, disproportionately affect our veterans. The reasons are not fully understood but might relate to differential risk factors and exposures among veterans compared to civilian populations.

Gastric cancer is potentially preventable but is almost certainly curable if detected at an early stage, which really provides the rationale for risk-based screening. Unfortunately, gastric cancer has not been a research priority and there are currently no prospective trials investigating patient outcomes associated with screening versus no screening, nor studies investigating surveillance versus no surveillance of conditions like atrophic gastritis and intestinal metaplasia or  defining appropriate surveillance and screening intervals.  The AGA recently published guidelines and clinical practice updates for intestinal metaplasia and atrophic gastritis management. But one common thread that these documents specifically called attention to, was the lack of high-quality data informing practice, especially practice in the United States. Other research priority areas include risk factors and risk stratification algorithms both for incident and fatal gastric cancer, as well as progression of atrophic gastritis and intestinal metaplasia. Having a better understanding of these factors would really help to fine tune our algorithms, and potentially identify factors that can even be intervened on to halt progression.

The last point that I'll highlight actually relates to non-H. pylori associated gastric cancer. We spend a lot of time focused on H. pylori associated gastric cancer, but an increasing number of gastric cancers are being diagnosed in people without evidence of H. pylori infection. Better understanding the interaction between genetic and environmental triggers and how this differs from H. pylori associated gastric cancer is critical to our approach to control and prevention since there certainly could be important nuances.

Dr. Shailja Shah is a gastroenterologist and clinical researcher at VA San Diego and the University of California, San Diego. Dr. Shah leads a multidisciplinary research program anchored in defining non-genetic, genetic, and systems-level determinants of H. pylori treatment- and disease-related clinical outcomes, including gastric cancer, among high-risk populations. She is also actively involved in research and public policy initiatives to promote gastric cancer prevention and early detection efforts. Dr. Shah’s current and prior sources of funding include the US Dept of Veterans Affairs, AHRQ, NIH, and the American Gastroenterological Association (AGA).

As a gastroenterologist and physician scientist at UCSD/VA San Diego and Moores Cancer Center, when you think about early detection and surveillance of gastric cancer, what are some of the signs and symptoms you look for and how would you factor in risk-based screenings?

Dr. Shah: In the United States, gastric cancer is overlooked because it is thought of as a rare cancer when, in fact, it's more common than esophageal cancer and in certain groups even approaches rates of colorectal cancer. This is important because we have clear guidelines on who to screen for esophageal and colorectal cancer, but we don't have these guidelines for gastric cancer.

The majority of gastric cancer cases in the United States is non-cardia gastric cancer, which refers to the location in the stomach that this type of cancer occurs. This is in comparison to gastric cancer of the cardia which makes up a much smaller percentage. I mention this up front because the risk factor profiles for these two cancers based on anatomic location are different. Cardia gastric cancer mostly tracks with risk factors for esophageal adenocarcinoma while non-cardia gastric cancer is more common in non-white groups who share a disproportionate burden—with some groups as much as 13.5-fold higher than non-Hispanic whites.

The key to the discussion of risk-based screening for non-cardia gastric cancer is that gastric cancer is typically asymptomatic or presents with only non-specific symptoms until it's in the more advanced stages. There's no cure for gastric cancer once it is in this advanced stage, which is really when symptoms prompt the diagnostic workup. When gastric cancer is caught in the early stage where it is asymptomatic or associated with non-specific symptoms that might not prompt an immediate diagnostic workup—this is the stage that resection would be curative.

There are countries such as Japan and South Korea where endoscopic screening for gastric cancer routinely occurs. This has translated into significant reductions in gastric cancer mortality, although notably has not substantially decreased the actual incidence of cancer. This again suggests that the benefit is early detection and the opportunity for curative resection—which can be accomplished either endoscopically or surgically. The United States population overall is not universally high risk for gastric cancer; however, there are certain identifiable high-risk groups who might benefit from endoscopy for early detection. These include non-white groups and immigrants from high risk countries for gastric cancer, people with a family history of gastric cancer, as well as people with gastric precancerous changes such as atrophic gastritis and intestinal metaplasia. These precancerous changes most often are the result of chronic H. pylori infection.

We don't have very precise risk stratification models, and this is a much-needed area of research. We do, however, have evidence from cost-effectiveness analyses that upper endoscopy for gastric cancer screening at the time of colonoscopy for colorectal cancer screening might be cost effective for non-white race and ethnic groups. At the very least, data from these modeling studies can form a starting point when we think of risk-based screening; ideally, we will have data from prospective studies to guide our approach to gastric cancer screening.

Since H. pylori is one of the strongest risk factors for non-cardia gastric cancer, what is your detailed approach to diagnosis and management?

Dr. Shah: H. pylori is a gram-negative bacterium and, globally, it is the most common chronic bacterial infection. Some studies estimate that over half the world's population is infected with H. pylori. It is difficult to get a precise estimate of the global burden of H. pylori, since many times this infection is asymptomatic and it is not one that is routinely screened for in most parts of the world, including the United States. Generally, testing for H. pylori is triggered by GI symptoms such as dyspepsia, abdominal discomfort, or in patients who don't have symptoms, the things that might trigger testing would be a family history of gastric cancer, unexplained iron deficiency, long term NSAID use, and a few other situations.

It is important to diagnose H. pylori because chronic untreated infection is associated with gastric inflammation, which in some cases can progress to loss of the normal gastric glands, a condition known as atrophic gastritis, and, if replaced by intestinal-type tissue, intestinal metaplasia. Such conditions are associated with significantly higher risk of gastric dysplasia and cancer, particularly if there is ongoing H. pylori infection. This stepwise cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric adenocarcinoma is known as the correa cascade, for which H. pylori is the most common trigger.

We know that H. pylori eradication with antibiotics and high dose acid suppression does improve that inflammation and reduces the risk of gastric cancer. But the key here is that the biggest benefit of H. pylori eradication is eradicating H. pylori prior to the development severe atrophic gastritis and intestinal metaplasia. Therefore, simply testing and treating for H. pylori is not enough for gastric cancer prevention since some people might already have these advanced changes, since these typically don't cause symptoms. This forms the basis for endoscopic surveillance of these precancerous conditions, which is detailed in the most recent AGA guidelines and clinical practice update on intestinal metaplasia and atrophic gastritis, respectively.

H. pylori eradication still a cornerstone of gastric cancer prevention and risk reduction. Careful treatment selection and ensuring that eradication is confirmed warrants emphasis, particularly in the face of rising rates of H. pylori eradication failure. My key takeaway points for H. pylori eradication therapy is that prior to prescribing treatment, it's very important to review patients prior antibiotic exposures specifically macrolides and fluoroquinolones, since patients who have had treatment with these antibiotics for any condition are more likely to be colonized with resistant H. pylori strains. Clarithromycin-triple therapy should not be used unless patients are confirmed to be colonized with clarithromycin susceptible H. pylori. Bismuth-based quadruple therapy is really the preferred first line treatment instead of clarithromycin-based triple therapy given the high rates of clarithromycin resistance. It's also important to provide patients with anticipatory guidance regarding both the importance of completing the full course, as well as some expected possible side effects of antibiotics such as GI upset, nausea. The other tenant therapy is ensuring appropriate gastric acid suppression, which is a point emphasized in the recently published AGA clinical practice update on H. pylori management. All patients should have repeat non-serological H. pylori testing to ensure that eradication was successful. To reduce false positive or false negative results, this repeat testing should be done at least 2-4 weeks after completion of therapy and with patients off PPI therapy for at least 1-2 weeks.

What have you found to be some of the key disparities in gastric cancer particularly as it pertains to the racial and ethnic groups in the United States?

Dr. Shah: Racial and ethnic differences in gastric cancer incidence is a defining factor for gastric cancer in the United States. Our team recently conducted a population-based analysis of the California Cancer Registry, which is one of, if not the largest and most diverse of the SEER cancer registries. The results of this study highlighted the disparity in risk of gastric cancer based on race/ethnicity. All non-white groups in the US had a significantly higher risk of non-cardia gastric cancer compared to non-Hispanic whites. This was particularly striking in the age group that we generally consider for cancer screening, where there was anywhere from 2-fold up to 13.5-fold higher risk of non-cardia gastric cancer compared to the reference non-Hispanic whites. In some of these groups for example, Korean American men above the age of 50, these rates were on par with colorectal cancer rates. Even more concerning, it is possible that these estimates are actually underestimating the true burden of disease, since early cancer is asymptomatic most of the time and might go undiagnosed in the absence of screening.

We also know that immigrants from countries where gastric cancer incidence is high, also retain that increased risk and mortality even when they immigrate to countries gastric cancer incidence is low overall. Admittedly, this risk varies depending on immigrant generation and level of acculturation, including dietary practices, and other factors. The risk is observed to decrease over subsequent generations and depending on acculturation, which underscores opportunities for research into interventions and initiatives to address modifiable risk factors.

Given that immigrants from countries of high gastric cancer, including Asian Americans and Hispanics, comprise the vast majority of population growth in the United States, the public health implications are enormous if we continue to be complacent on gastric cancer prevention and early detection efforts.

As the fifth most common cancer and the third most common cause of cancer related deaths, based on recent studies and your personal experiences as a medical practitioner, also considering the gastric cancer does not cause symptoms until it is in the advanced stage, what are your recommendations as it relates to early detection and improving gastric cancer related outcomes?

Dr. Shah: The first step in my opinion, is recognizing that gastric cancer disproportionately affects certain populations in the US like I mentioned, especially racial and ethnic minorities and other under-represented populations, including US veterans. As a VA clinician and a VA investigator, we see that risk factors for gastric cancer, including H. pylori, disproportionately affect our veterans. The reasons are not fully understood but might relate to differential risk factors and exposures among veterans compared to civilian populations.

Gastric cancer is potentially preventable but is almost certainly curable if detected at an early stage, which really provides the rationale for risk-based screening. Unfortunately, gastric cancer has not been a research priority and there are currently no prospective trials investigating patient outcomes associated with screening versus no screening, nor studies investigating surveillance versus no surveillance of conditions like atrophic gastritis and intestinal metaplasia or  defining appropriate surveillance and screening intervals.  The AGA recently published guidelines and clinical practice updates for intestinal metaplasia and atrophic gastritis management. But one common thread that these documents specifically called attention to, was the lack of high-quality data informing practice, especially practice in the United States. Other research priority areas include risk factors and risk stratification algorithms both for incident and fatal gastric cancer, as well as progression of atrophic gastritis and intestinal metaplasia. Having a better understanding of these factors would really help to fine tune our algorithms, and potentially identify factors that can even be intervened on to halt progression.

The last point that I'll highlight actually relates to non-H. pylori associated gastric cancer. We spend a lot of time focused on H. pylori associated gastric cancer, but an increasing number of gastric cancers are being diagnosed in people without evidence of H. pylori infection. Better understanding the interaction between genetic and environmental triggers and how this differs from H. pylori associated gastric cancer is critical to our approach to control and prevention since there certainly could be important nuances.

Dr. Shailja Shah is a gastroenterologist and clinical researcher at VA San Diego and the University of California, San Diego. Dr. Shah leads a multidisciplinary research program anchored in defining non-genetic, genetic, and systems-level determinants of H. pylori treatment- and disease-related clinical outcomes, including gastric cancer, among high-risk populations. She is also actively involved in research and public policy initiatives to promote gastric cancer prevention and early detection efforts. Dr. Shah’s current and prior sources of funding include the US Dept of Veterans Affairs, AHRQ, NIH, and the American Gastroenterological Association (AGA).

As a gastroenterologist and physician scientist at UCSD/VA San Diego and Moores Cancer Center, when you think about early detection and surveillance of gastric cancer, what are some of the signs and symptoms you look for and how would you factor in risk-based screenings?

Dr. Shah: In the United States, gastric cancer is overlooked because it is thought of as a rare cancer when, in fact, it's more common than esophageal cancer and in certain groups even approaches rates of colorectal cancer. This is important because we have clear guidelines on who to screen for esophageal and colorectal cancer, but we don't have these guidelines for gastric cancer.

The majority of gastric cancer cases in the United States is non-cardia gastric cancer, which refers to the location in the stomach that this type of cancer occurs. This is in comparison to gastric cancer of the cardia which makes up a much smaller percentage. I mention this up front because the risk factor profiles for these two cancers based on anatomic location are different. Cardia gastric cancer mostly tracks with risk factors for esophageal adenocarcinoma while non-cardia gastric cancer is more common in non-white groups who share a disproportionate burden—with some groups as much as 13.5-fold higher than non-Hispanic whites.

The key to the discussion of risk-based screening for non-cardia gastric cancer is that gastric cancer is typically asymptomatic or presents with only non-specific symptoms until it's in the more advanced stages. There's no cure for gastric cancer once it is in this advanced stage, which is really when symptoms prompt the diagnostic workup. When gastric cancer is caught in the early stage where it is asymptomatic or associated with non-specific symptoms that might not prompt an immediate diagnostic workup—this is the stage that resection would be curative.

There are countries such as Japan and South Korea where endoscopic screening for gastric cancer routinely occurs. This has translated into significant reductions in gastric cancer mortality, although notably has not substantially decreased the actual incidence of cancer. This again suggests that the benefit is early detection and the opportunity for curative resection—which can be accomplished either endoscopically or surgically. The United States population overall is not universally high risk for gastric cancer; however, there are certain identifiable high-risk groups who might benefit from endoscopy for early detection. These include non-white groups and immigrants from high risk countries for gastric cancer, people with a family history of gastric cancer, as well as people with gastric precancerous changes such as atrophic gastritis and intestinal metaplasia. These precancerous changes most often are the result of chronic H. pylori infection.

We don't have very precise risk stratification models, and this is a much-needed area of research. We do, however, have evidence from cost-effectiveness analyses that upper endoscopy for gastric cancer screening at the time of colonoscopy for colorectal cancer screening might be cost effective for non-white race and ethnic groups. At the very least, data from these modeling studies can form a starting point when we think of risk-based screening; ideally, we will have data from prospective studies to guide our approach to gastric cancer screening.

Since H. pylori is one of the strongest risk factors for non-cardia gastric cancer, what is your detailed approach to diagnosis and management?

Dr. Shah: H. pylori is a gram-negative bacterium and, globally, it is the most common chronic bacterial infection. Some studies estimate that over half the world's population is infected with H. pylori. It is difficult to get a precise estimate of the global burden of H. pylori, since many times this infection is asymptomatic and it is not one that is routinely screened for in most parts of the world, including the United States. Generally, testing for H. pylori is triggered by GI symptoms such as dyspepsia, abdominal discomfort, or in patients who don't have symptoms, the things that might trigger testing would be a family history of gastric cancer, unexplained iron deficiency, long term NSAID use, and a few other situations.

It is important to diagnose H. pylori because chronic untreated infection is associated with gastric inflammation, which in some cases can progress to loss of the normal gastric glands, a condition known as atrophic gastritis, and, if replaced by intestinal-type tissue, intestinal metaplasia. Such conditions are associated with significantly higher risk of gastric dysplasia and cancer, particularly if there is ongoing H. pylori infection. This stepwise cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric adenocarcinoma is known as the correa cascade, for which H. pylori is the most common trigger.

We know that H. pylori eradication with antibiotics and high dose acid suppression does improve that inflammation and reduces the risk of gastric cancer. But the key here is that the biggest benefit of H. pylori eradication is eradicating H. pylori prior to the development severe atrophic gastritis and intestinal metaplasia. Therefore, simply testing and treating for H. pylori is not enough for gastric cancer prevention since some people might already have these advanced changes, since these typically don't cause symptoms. This forms the basis for endoscopic surveillance of these precancerous conditions, which is detailed in the most recent AGA guidelines and clinical practice update on intestinal metaplasia and atrophic gastritis, respectively.

H. pylori eradication still a cornerstone of gastric cancer prevention and risk reduction. Careful treatment selection and ensuring that eradication is confirmed warrants emphasis, particularly in the face of rising rates of H. pylori eradication failure. My key takeaway points for H. pylori eradication therapy is that prior to prescribing treatment, it's very important to review patients prior antibiotic exposures specifically macrolides and fluoroquinolones, since patients who have had treatment with these antibiotics for any condition are more likely to be colonized with resistant H. pylori strains. Clarithromycin-triple therapy should not be used unless patients are confirmed to be colonized with clarithromycin susceptible H. pylori. Bismuth-based quadruple therapy is really the preferred first line treatment instead of clarithromycin-based triple therapy given the high rates of clarithromycin resistance. It's also important to provide patients with anticipatory guidance regarding both the importance of completing the full course, as well as some expected possible side effects of antibiotics such as GI upset, nausea. The other tenant therapy is ensuring appropriate gastric acid suppression, which is a point emphasized in the recently published AGA clinical practice update on H. pylori management. All patients should have repeat non-serological H. pylori testing to ensure that eradication was successful. To reduce false positive or false negative results, this repeat testing should be done at least 2-4 weeks after completion of therapy and with patients off PPI therapy for at least 1-2 weeks.

What have you found to be some of the key disparities in gastric cancer particularly as it pertains to the racial and ethnic groups in the United States?

Dr. Shah: Racial and ethnic differences in gastric cancer incidence is a defining factor for gastric cancer in the United States. Our team recently conducted a population-based analysis of the California Cancer Registry, which is one of, if not the largest and most diverse of the SEER cancer registries. The results of this study highlighted the disparity in risk of gastric cancer based on race/ethnicity. All non-white groups in the US had a significantly higher risk of non-cardia gastric cancer compared to non-Hispanic whites. This was particularly striking in the age group that we generally consider for cancer screening, where there was anywhere from 2-fold up to 13.5-fold higher risk of non-cardia gastric cancer compared to the reference non-Hispanic whites. In some of these groups for example, Korean American men above the age of 50, these rates were on par with colorectal cancer rates. Even more concerning, it is possible that these estimates are actually underestimating the true burden of disease, since early cancer is asymptomatic most of the time and might go undiagnosed in the absence of screening.

We also know that immigrants from countries where gastric cancer incidence is high, also retain that increased risk and mortality even when they immigrate to countries gastric cancer incidence is low overall. Admittedly, this risk varies depending on immigrant generation and level of acculturation, including dietary practices, and other factors. The risk is observed to decrease over subsequent generations and depending on acculturation, which underscores opportunities for research into interventions and initiatives to address modifiable risk factors.

Given that immigrants from countries of high gastric cancer, including Asian Americans and Hispanics, comprise the vast majority of population growth in the United States, the public health implications are enormous if we continue to be complacent on gastric cancer prevention and early detection efforts.

As the fifth most common cancer and the third most common cause of cancer related deaths, based on recent studies and your personal experiences as a medical practitioner, also considering the gastric cancer does not cause symptoms until it is in the advanced stage, what are your recommendations as it relates to early detection and improving gastric cancer related outcomes?

Dr. Shah: The first step in my opinion, is recognizing that gastric cancer disproportionately affects certain populations in the US like I mentioned, especially racial and ethnic minorities and other under-represented populations, including US veterans. As a VA clinician and a VA investigator, we see that risk factors for gastric cancer, including H. pylori, disproportionately affect our veterans. The reasons are not fully understood but might relate to differential risk factors and exposures among veterans compared to civilian populations.

Gastric cancer is potentially preventable but is almost certainly curable if detected at an early stage, which really provides the rationale for risk-based screening. Unfortunately, gastric cancer has not been a research priority and there are currently no prospective trials investigating patient outcomes associated with screening versus no screening, nor studies investigating surveillance versus no surveillance of conditions like atrophic gastritis and intestinal metaplasia or  defining appropriate surveillance and screening intervals.  The AGA recently published guidelines and clinical practice updates for intestinal metaplasia and atrophic gastritis management. But one common thread that these documents specifically called attention to, was the lack of high-quality data informing practice, especially practice in the United States. Other research priority areas include risk factors and risk stratification algorithms both for incident and fatal gastric cancer, as well as progression of atrophic gastritis and intestinal metaplasia. Having a better understanding of these factors would really help to fine tune our algorithms, and potentially identify factors that can even be intervened on to halt progression.

The last point that I'll highlight actually relates to non-H. pylori associated gastric cancer. We spend a lot of time focused on H. pylori associated gastric cancer, but an increasing number of gastric cancers are being diagnosed in people without evidence of H. pylori infection. Better understanding the interaction between genetic and environmental triggers and how this differs from H. pylori associated gastric cancer is critical to our approach to control and prevention since there certainly could be important nuances.