Publications by authors named "Shailja C Shah"

52 Publications

The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review.

Therap Adv Gastroenterol 2021 31;14:17562848211004493. Epub 2021 Mar 31.

Section of Gastroenterology, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN.

The inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens - a common cause of dysbiosis - have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as , and parasites, such as species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.
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http://dx.doi.org/10.1177/17562848211004493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020742PMC
March 2021

Gastric cancer: a neglected threat to racial and ethnic minorities in the USA.

Authors:
Shailja C Shah

Lancet Gastroenterol Hepatol 2021 04;6(4):266-267

Gastroenterology Section, Tennessee Valley Healthcare System, Veterans Health Administration, Nashville TN, USA; Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN 37203, USA. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(21)00064-9DOI Listing
April 2021

AGA Clinical Practice Update on the Management of Refractory Helicobacter pylori Infection: Expert Review.

Gastroenterology 2021 Apr 29;160(5):1831-1841. Epub 2021 Jan 29.

Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

The purpose of this CPU Expert Review is to provide clinicians with guidance on the management of Helicobacter pylori after an initial attempt at eradication therapy fails, including best practice advice on specific regimen selection, and consideration of patient and systems factors that contribute to treatment efficacy. This Expert Review is not a formal systematic review, but is based upon a review of the literature to provide practical advice. No formal rating of the strength or quality of the evidence was carried out. Accordingly, a combination of available evidence and consensus-based expert opinion were used to develop these best practice advice statements.
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http://dx.doi.org/10.1053/j.gastro.2020.11.059DOI Listing
April 2021

Magnesium intake is associated with a reduced risk of incident liver cancer, based on an analysis of the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort.

Am J Clin Nutr 2021 03;113(3):630-638

Division of Epidemiology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Liver cancer incidence and mortality are escalating globally. Magnesium intake has been studied extensively in nonmalignant liver pathology, but the association between dietary intake of magnesium and primary liver malignancy has not been previously evaluated.

Objectives: We aimed to determine the association between total magnesium intake and primary liver cancer risk.

Methods: Using the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort, we estimated the association between magnesium intake and the risk of incident primary liver cancer using Cox proportional hazard modeling adjusted for relevant confounders. Comprehensive stratified and sensitivity analyses were performed.

Results: During 6.4 million person-years of follow-up time, 1067 primary liver cancers occurred in 536,359 participants. Higher magnesium intake was independently associated with a lower risk of liver cancer (P-trend = 0.005), with intakes in the highest compared with lowest quartile associated with 35% lower risk (HR: 0.65; 95% CI: 0.48, 0.87). The dose-related inverse association was more pronounced in moderate and heavy alcohol users (HR: 0.54; 95% CI: 0.35, 0.82; P-trend = 0.006), and this interaction was statistically significant (P-interaction = 0.04).

Conclusions: Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users. Robust experimental and mechanistic data provide a biological basis to support these findings.
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http://dx.doi.org/10.1093/ajcn/nqaa326DOI Listing
March 2021

Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study in South Korea.

Clin Gastroenterol Hepatol 2020 Oct 1. Epub 2020 Oct 1.

Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea. Electronic address:

Background & Aims: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship.

Methods: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs.

Results: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs.

Conclusions: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors.
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http://dx.doi.org/10.1016/j.cgh.2020.09.054DOI Listing
October 2020

Population-Based Analysis of Differences in Gastric Cancer Incidence Among Races and Ethnicities in Individuals Age 50 Years and Older.

Gastroenterology 2020 11 6;159(5):1705-1714.e2. Epub 2020 Aug 6.

Greater Bay Area Cancer Registry, University of California San Francisco, San Francisco, California; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.

Background & Aims: There are racial and ethnic differences in the incidence of gastric adenocarcinoma worldwide and in the US. Based on a decision analysis, screening for noncardia gastric adenocarcinoma might be cost-effective for non-White individuals 50 years or older. However, a lack of precise, contemporary information on gastric adenocarcinoma incidence in specific anatomic sites for this age group has impeded prevention and early detection programs in the US. We aimed to estimate the differences in gastric adenocarcinoma incidence in specific anatomic sites among races and ethnicities in individuals 50 years or older.

Methods: We analyzed California Cancer Registry data from 2011 through 2015 to estimate incidences of gastric adenocarcinoma in specific anatomic sites for non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 7 largest Asian American populations. We calculated the differential incidence between non-White groups and NHW using incidence rate ratios and 95% confidence intervals (CIs).

Results: Compared with NHW subjects, all non-White groups had significantly higher incidences of noncardia gastric adenocarcinoma; the incidence was highest among Korean American men 50 years and older (70 cases per 100,000). Compared with NHW subjects 50 years and older, the risk of noncardia gastric adenocarcinoma was 1.8-fold (95% CI, 1.37-2.31) to 7.3-fold (95% CI, 5.73-9.19) higher in most non-White groups and 12.0-fold (95% CI, 9.96-14.6) to 14.5-fold (95% CI, 12.5-16.9) higher among Korean American men and women 50 years and older, respectively. Compared with NHW men 50 years and older, all non-White men, except Japanese and Korean American men, had a significantly lower risk of cardia gastric adenocarcinoma.

Conclusions: We identified several-fold differences in incidences of gastric adenocarcinoma in specific anatomic sites among racial and ethnic groups, with significant age and sex differences. These findings can be used to develop targeted risk reduction programs for gastric adenocarcinoma.
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http://dx.doi.org/10.1053/j.gastro.2020.07.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680373PMC
November 2020

Decision model analyses of upper endoscopy for gastric cancer screening and preneoplasia surveillance: a systematic review.

Therap Adv Gastroenterol 2020 16;13:1756284820941662. Epub 2020 Jul 16.

Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, Medical Research Building IV, Room 1030-C (mail), Nashville, TN 37232-0252, USA.

Aims: Gastric cancer (GC) is the third leading cause of cancer death worldwide, but the burden of disease is not distributed evenly. GC screening routinely occurs in some high-incidence regions/countries and is generally cost-effective, which is attributed largely to the associated GC mortality reduction. In regions of low-intermediate incidence, less is known about the outcomes of GC screening and gastric precancer surveillance, including cost-effectiveness, since there are no comparative clinical studies. Decision analytic studies are informative in such instances where logistical limitations preclude "gold standard" study designs. We therefore aimed to conduct a systematic review of decision model analyses focused on endoscopic GC screening or precancer surveillance.

Methods: We identified decision model analyses, including cost effectiveness and cost utility studies, of GC screening or preneoplasia surveillance. At minimum, articles were evaluated for: study country; analytic design; population and health states; time horizon; model assumptions; outcomes; threshold value(s) for "cost-effective" determination; and sensitivity analyses. Quality appraisal was performed using a modified Drummond's analytic scoring system. Data sources were PubMed, Web of Science, Embase, and the Cochrane Library.

Results: We identified 17 studies (8 screening, 4 surveillance, and 5 screening and surveillance) that met full inclusion criteria. Endoscopic screening in countries of high GC incidence was cost-effective across all studies; targeted screening of high-risk populations within otherwise low-intermediate incidence countries was also generally cost-effective. Surveillance of gastric precancer, including atrophic gastritis or gastric intestinal metaplasia, was generally cost-effective. Most studies had high appraisal scores, with 4 (24%) studies achieving perfect scores on the Drummond scale.

Conclusion: Decision model analyses offer a unique mechanism with which to efficiently explore the cost benefit of various prevention and early detection strategies. Based on this comprehensive systematic review, upper endoscopy for GC screening and gastric precancer surveillance might be cost-effective depending on the population and protocol. Focused efforts are especially needed not only to define the optimal approach, but also to define the populations within otherwise low-intermediate regions/countries who might benefit most.
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http://dx.doi.org/10.1177/1756284820941662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366398PMC
July 2020

Endoscopy for Gastric Cancer Screening Is Cost Effective for Asian Americans in the United States.

Clin Gastroenterol Hepatol 2020 12 21;18(13):3026-3039. Epub 2020 Jul 21.

Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background & Aims: Endoscopic screening for gastric cancer is routine in some countries with high incidence and is associated with reduced gastric cancer-related mortality. Immigrants from countries of high incidence to low incidence of gastric cancer retain their elevated risk, but no screening recommendations have been made for these groups in the United States. We aimed to determine the cost effectiveness of different endoscopic screening strategies for noncardia gastric cancer, compared with no screening, among Chinese, Filipino, Southeast Asian, Vietnamese, Korean, and Japanese Americans.

Methods: We generated a decision-analytic Markov model to simulate a cohort of asymptomatic 50-year-old Asian Americans. The cost effectiveness of 2 distinct strategies for endoscopic gastric cancer screening was compared with no screening for each group, stratified by sex. Outcome measures were reported in incremental cost-effectiveness ratios (ICERs), with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). Extensive sensitivity analyses were performed.

Results: Compared with performing no endoscopic gastric cancer screening, performing a 1-time upper endoscopy with biopsies, with continued endoscopic surveillance if gastric intestinal metaplasia was identified, was cost effective, whereas performing ongoing biennial endoscopies, even for patients with normal findings from endoscopy and histopathology, was not. The lowest ICERs were observed for Chinese, Japanese, and Korean Americans (all <$73,748/QALY).

Conclusions: Endoscopic screening for gastric cancer with ongoing surveillance of gastric preneoplasia is cost effective for Asian Americans ages 50 years or older in the United States. The lowest ICERs were for Chinese, Japanese, and Korean Americans (all <$73,748/QALY).
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http://dx.doi.org/10.1016/j.cgh.2020.07.031DOI Listing
December 2020

Diagnosis and management of inflammatory bowel disease-associated neoplasia: considerations in the modern era.

Therap Adv Gastroenterol 2020 6;13:1756284820920779. Epub 2020 May 6.

Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, 10th floor Rm 1030-C, 2215 Garland Avenue, Medical Research Building IV, Nashville, TN 37203, USA.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing intestinal neoplasia-particularly colorectal neoplasia, including dysplasia and colorectal cancer (CRC)-as a primary consequence of chronic inflammation. While the current incidence of CRC in IBD is lower compared with prior decades, due, in large part, to more effective therapies and improved colonoscopic technologies, CRC still accounts for a significant proportion of IBD-related deaths. The focus of this review is on the pathogenesis; epidemiology, including disease- and patient-related risk factors; diagnosis; surveillance; and management of IBD-associated neoplasia.
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http://dx.doi.org/10.1177/1756284820920779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236570PMC
May 2020

Sex-based differences in inflammatory bowel diseases: a review.

Therap Adv Gastroenterol 2020 28;13:1756284820915043. Epub 2020 Apr 28.

Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, Medical Research Building IV, Room 1030-C (Mail), Nashville, TN 37240-0002, USA.

Sex-based differences in inflammatory bowel disease (IBD) pathogenesis, disease course, and response to therapy have been increasingly recognized, however, not fully understood. Experimental and translational models have been leveraged to investigate hypothesized mechanisms for these observed differences, including the potential modifying role of sex hormones and sex-dependent (epi)genetic and gut microbiome changes. The primary objective of this review is to comprehensively describe sex-based differences in IBD including epidemiology, pathogenesis, phenotypic differences, therapeutic response, and outcomes.
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http://dx.doi.org/10.1177/1756284820915043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236567PMC
April 2020

County Rurality and Socioeconomic Deprivation Is Associated With Reduced Survival From Gastric Cancer in the United States.

Gastroenterology 2020 10 7;159(4):1555-1557.e2. Epub 2020 May 7.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1053/j.gastro.2020.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577922PMC
October 2020

Systematic review: gastrointestinal infection and incident inflammatory bowel disease.

Aliment Pharmacol Ther 2020 06 5;51(12):1222-1232. Epub 2020 May 5.

Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: The initiating events of chronic gastrointestinal (GI) inflammation in Crohn's disease (CD) and ulcerative colitis (UC) are not well-defined, but GI infections are implicated.

Aims: To define the role of GI infections in risk of incident inflammatory bowel disease (IBD) and synthesise the current body of relevant translational data to provide biological context for associations between GI infections and IBD risk.

Methods: We systematically reviewed electronic databases through February 2020. Clinical studies that provided risk estimates of the association between GI infections and incident IBD were included. Inclusion criteria were broader for translational studies aiming to define mechanisms of GI infections and predisposition to or protection from IBD.

Results: Of the studies identified, 63 met full inclusion criteria. Among studies of clinical gastroenteritis, bacteria-specifically, Salmonella species, Campylobacter species and Clostridioides difficile-demonstrated consistent positive associations with risk of incident IBD. Of viruses, norovirus was associated with increased risk of incident CD. Regarding inverse associations with incident IBD, Helicobacter pylori and helminth infections were associated with a generally consistent reduced risk of IBD. Based on a qualitative analysis of the translational data, putative mechanisms involve multiple microbial and immunologic pathways.

Conclusions: Based on this systematic review, certain enteric pathogens are associated with an increased risk of incident IBD, while others are potentially protective. Prospective studies are required to clarify the clinical implications of these enteric pathogens on the risk and course of IBD, and possible therapeutic or preventative benefit.
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http://dx.doi.org/10.1111/apt.15770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354095PMC
June 2020

Associations between calcium and magnesium intake and the risk of incident oesophageal cancer: an analysis of the NIH-AARP Diet and Health Study prospective cohort.

Br J Cancer 2020 06 3;122(12):1857-1864. Epub 2020 Apr 3.

Division of Epidemiology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Risk reduction through dietary modifications is an adjunct strategy for prevention of oesophageal cancer, a leading cause of cancer-related mortality and morbidity worldwide. We aimed to estimate the association between calcium and magnesium intakes and incident oesophageal cancer (OC).

Methods: We conducted a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort. We used multivariable Cox proportional hazard modeling to estimate the association between total intakes and incident OC overall and by histology (oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC)). Sensitivity and stratified analyses were performed.

Results: Among 536,359 included respondents, 1414 incident OCs occurred over 6.5 million person-years follow-up time. Increasing dietary calcium intake was associated with an adjusted 32-41% lower risk of OSCC compared to the lowest quartile (p-trend 0.01). There was a positive association between increasing magnesium intake and OAC risk, but only among participants with low calcium:magnesium intake ratios (p-trend 0.04). There was a significant interaction with smoking status.

Conclusions: Based on a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort, dietary intakes of calcium and magnesium were significantly associated with risk of OSCC and, among certain participants, OAC, respectively. If validated, these findings could inform dietary modifications among at-risk individuals. Mechanistic investigations would provide additional insight.
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http://dx.doi.org/10.1038/s41416-020-0818-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283350PMC
June 2020

Reappraising Risk Factors for Inflammatory Bowel Disease-associated Neoplasia: Implications for Colonoscopic Surveillance in IBD.

J Crohns Colitis 2020 Sep;14(8):1172-1177

Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

One of the most feared complications of inflammatory bowel disease [IBD]-associated colitis is colorectal cancer. When considering the substantial increase in the prevalence of IBD, without any anticipated decline, coupled with decreasing colectomy rates for dysplasia and expanding medical options for effectively controlling inflammation, it is predicted that the pool of people living with-and ageing with-colonic IBD, who are recommended to undergo lifelong colonoscopic surveillance for colorectal neoplasia, will strain existing resources and challenge the sustainability of current guideline-based surveillance recommendations. At the same time, we are missing the opportunity for early detection in a group that is overlooked as high-risk, as a substantial proportion of colorectal cancers are being diagnosed in individuals with colonic IBD who have disease duration shorter than when guidelines recommend surveillance initiation. Here, we reappraise: 1] inflammation as a dynamic risk factor that considers patients' cumulative course; 2] time of screening initiation that is not based primarily on absolute disease duration; and 3] surveillance intervals as an iterative determination based on individual patient factors and consecutive colonoscopic findings. This Viewpoint supports a paradigm shift that will ideally result in a more effective and higher-value colorectal cancer prevention approach in IBD.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa040DOI Listing
September 2020

Surveillance of Gastric Intestinal Metaplasia.

Am J Gastroenterol 2020 05;115(5):641-644

Department of Gastroenterology, Kaiser Permanente Santa Clara Medical Center, Santa Clara, California, USA.

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http://dx.doi.org/10.14309/ajg.0000000000000540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364865PMC
May 2020

Spotlight: Gastric Intestinal Metaplasia.

Gastroenterology 2020 02;158(3):704

Salt Lake City Specialty Care Center of Innovation & Gastroenterology Section, VA Salt Lake City Health Care System, Salt Lake City, UT.

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http://dx.doi.org/10.1053/j.gastro.2020.01.012DOI Listing
February 2020

Occupational exposures and odds of gastric cancer: a StoP project consortium pooled analysis.

Int J Epidemiol 2020 04;49(2):422-434

Tisch Cancer Institute, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to determine the association between occupations/occupational exposures and odds of gastric cancer.

Methods: We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project. Multivariable logistic regression was used to estimate the odds ratio (OR) of gastric cancer adjusted for relevant confounders.

Results: A total of 5279 gastric cancer cases and 12 297 controls were analysed. There were higher odds of gastric cancer among labour-related occupations, including: agricultural and animal husbandry workers [odds ratio (OR) 1.33, 95% confidence interval (CI): 1.06-1.68]; miners, quarrymen, well-drillers and related workers (OR 1.70, 95% CI: 1.01-2.88); blacksmiths, toolmakers and machine-tool operators (OR 1.41, 95% CI: 1.05-1.89); bricklayers, carpenters and construction workers (OR 1.30, 95% CI: 1.06-1.60); and stationary engine and related equipment operators (OR 6.53, 95% CI: 1.41-30.19). The ORs for wood-dust exposure were 1.51 (95% CI: 1.01-2.26) for intestinal-type and 2.52 (95% CI: 1.46-4.33) for diffuse-type gastric cancer. Corresponding values for aromatic amine exposure were 1.83 (95% CI: 1.09-3.06) and 2.92 (95% CI: 1.36-6.26). Exposure to coal derivatives, pesticides/herbicides, chromium, radiation and magnetic fields were associated with higher odds of diffuse-type, but not intestinal-type gastric cancer.

Conclusions: Based on a large pooled analysis, we identified several occupations and related exposures that are associated with elevated odds of gastric cancer. These findings have potential implications for risk attenuation and could be used to direct investigations evaluating the impact of targeted gastric cancer prevention/early detection programmes based on occupation.
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http://dx.doi.org/10.1093/ije/dyz263DOI Listing
April 2020

Histologic Subtyping of Gastric Intestinal Metaplasia: Overview and Considerations for Clinical Practice.

Gastroenterology 2020 02 6;158(3):745-750. Epub 2019 Dec 6.

Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.

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http://dx.doi.org/10.1053/j.gastro.2019.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302270PMC
February 2020

Advancing the Science in Gastric Pre-Neoplasia: Study Design Considerations.

Gastroenterology 2020 02 6;158(3):751-759. Epub 2019 Dec 6.

Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2019.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354093PMC
February 2020

AGA Technical Review on Gastric Intestinal Metaplasia-Epidemiology and Risk Factors.

Gastroenterology 2020 02 6;158(3):732-744.e16. Epub 2019 Dec 6.

Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, Kansas.

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http://dx.doi.org/10.1053/j.gastro.2019.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425600PMC
February 2020

AGA Technical Review on Gastric Intestinal Metaplasia-Natural History and Clinical Outcomes.

Gastroenterology 2020 02 6;158(3):705-731.e5. Epub 2019 Dec 6.

Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, Kansas.

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http://dx.doi.org/10.1053/j.gastro.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375032PMC
February 2020

Associations between calcium and magnesium intake and the risk of incident gastric cancer: A prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study.

Int J Cancer 2020 06 12;146(11):2999-3010. Epub 2019 Oct 12.

Division of Epidemiology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.

Gastric cancer remains a leading cause of cancer-related mortality. Identifying dietary and other modifiable disease determinants has important implications for risk attenuation in susceptible individuals. Our primary aim was to estimate the association between dietary and supplemental intakes of calcium and magnesium and the risk of incident gastric cancer. We conducted a prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons Diet and Health Study. We used Cox proportional hazard modeling to estimate the association between calcium and magnesium intakes with risk of incident gastric adenocarcinoma (GA) overall and by anatomic location, noncardia GA (NCGA) and cardia GA (CGA). A total of 536,403 respondents (59% males, 41% females) were included for analysis, among whom 1,518 incident GAs (797 NCGA and 721 CGA) occurred. Increasing calcium intake was associated with lower risk of GA overall (p-trend = 0.05), driven primarily by the association with NCGA, where the above median calcium intakes were associated with a 23% reduction in risk compared to the lowest quartile (p-trend = 0.05). This magnitude of NCGA risk reduction was greater among nonwhite ethnic group and Hispanics (hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.24-1.07, p-trend = 0.04), current/former smokers (HR 0.58, 95% CI: 0.41-0.81), obese individuals (HR 0.54, 95% CI: 0.31-0.96) and those with high NCGA risk scores (HR 0.50, 95% CI: 0.31-0.80). Among men only, increasing magnesium intake was associated with 22-27% reduced risk of NCGA (p-trend = 0.05), while for the cohort, dietary magnesium intake in the highest vs. lowest quartile was associated with a 34% reduced risk of NCGA (HR 0.66, 95% CI: 0.48-0.90). These findings have important implications for risk factor modification. Future investigations are needed not only to confirm our results, but to define mechanisms underlying these associations.
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http://dx.doi.org/10.1002/ijc.32659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048631PMC
June 2020

Association Between Indefinite Dysplasia and Advanced Neoplasia in Patients With Inflammatory Bowel Diseases Undergoing Surveillance.

Clin Gastroenterol Hepatol 2020 06 22;18(7):1518-1527.e3. Epub 2019 Aug 22.

Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background & Aims: Little is known about the clinical significance of indefinite dysplasia (IND) in patients with inflammatory bowel diseases (IBD) undergoing colonoscopic surveillance for colorectal neoplasia.

Methods: We conducted a retrospective cohort analysis of 492 patients with colonic IBD for 8 or more years or concomitant primary sclerosing cholangitis, with no history of advanced colorectal neoplasia (high-grade dysplasia or colorectal cancer) or colectomy, undergoing colorectal neoplasia surveillance at a tertiary IBD referral center from 2001 through 2017. Subjects received consistent histopathologic grading of dysplasia. We collected data on time to development of (advanced) colorectal neoplasia or colectomy using Kaplan Meier methods. We identified factors independently associated with (advanced) colorectal neoplasia with multivariable Cox regression analysis.

Results: After 2149 person-years of follow-up, 53 patients (10.8%) received a diagnosis of IND without prior or synchronous low-grade dysplasia (LGD). Compared to patients without dysplasia, patients with IND had a significantly higher risk of advanced colorectal neoplasia (adjusted hazard ratio, 6.85; 95% CI, 1.78-26.4) and colorectal neoplasia (adjusted hazard ratio, 3.25; 95% CI, 1.50-7.05), but not colectomy (P = .78). Compared to IND, LGD was associated with a significantly higher risk of advanced colorectal neoplasia (P = .05). Following a diagnosis of no dysplasia, IND only, or LGD, the incidence rates of advanced colorectal neoplasia were 0.4% per patient-year, 3.1% per patient-year, and 8.4% per patient-year, respectively.

Conclusions: In a retrospective analysis of patients with IBD undergoing colorectal neoplasia surveillance with consistent histopathologic grading of dysplasia, IND was independently associated with a significant increase in risk of advanced colorectal neoplasia. These findings require validation and if confirmed, a reappraisal of the colorectal neoplasia surveillance guidelines.
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http://dx.doi.org/10.1016/j.cgh.2019.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354098PMC
June 2020

Friend or Foe in Inflammatory Bowel Disease Pathogenesis: Not All Infections Are Equal.

Authors:
Shailja C Shah

Gastroenterology 2019 11 20;157(5):1441-1442. Epub 2019 Aug 20.

Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.

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http://dx.doi.org/10.1053/j.gastro.2019.06.044DOI Listing
November 2019

Viewpoint: Inflammatory Bowel Diseases Among Immigrants From Low- to High-Incidence Countries: Opportunities and Considerations.

J Crohns Colitis 2020 Feb;14(2):267-273

Division of Gastroenterology, Vanderbilt University, Nashville TN, USA.

The inflammatory bowel diseases [IBDs], inclusive of Crohn's disease [CD] and ulcerative colitis [UC], are chronic, progressive immune-mediated diseases associated with high morbidity and substantial economic impact. The pathogenesis implicates a complex interaction between environmental determinants and genetic susceptibility. Of concern, the incidence and prevalence of IBD are increasing globally, with the highest relative increase observed in developing and recently developed countries. One high-risk yet underappreciated population is immigrants from countries of low to high IBD incidence, as evidenced by epidemiologic studies demonstrating higher risk of IBD among second- versus first-generation and younger versus older immigrants from low- to high-incidence countries [LTHICs]. The reasons underlying these emerging patterns among immigrants are incompletely understood and provide enormous opportunities to better define the pathophysiology of IBD and move toward disease prevention or at least earlier diagnosis. The rapidity of this epidemiologic shift in the demographic profile of IBD, which was traditionally a disease of Caucasians in industrialized countries, strongly implicates non-genetic factors and gene-environment interactions in the pathophysiology of IBD among immigrants from LTHICs. The primary objectives of this Viewpoint are to [1] provide a focused overview of IBD epidemiology among immigrants from countries at differential IBD risk; [2] emphasize the potential to advance our understanding of IBD pathogenesis via targeted research efforts to delineate risk and protective determinants in this cohort; and [3] highlight disparities and barriers in IBD care, as well as the economic implications of the rising, yet underappreciated, disease burden among immigrants from LTHICs.
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http://dx.doi.org/10.1093/ecco-jcc/jjz139DOI Listing
February 2020

Systematic review with meta-analysis: association between Helicobacter pylori CagA seropositivity and odds of inflammatory bowel disease.

Aliment Pharmacol Ther 2019 07 5;50(2):121-131. Epub 2019 Jun 5.

Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Accumulating data support a protective role of Helicobacter pylori against inflammatory bowel diseases (IBD), which might be mediated by strain-specific constituents, specifically cagA expression.

Aim: To perform a systematic review and meta-analysis to more clearly define the association between CagA seropositivity and IBD.

Methods: We identified comparative studies that included sufficient detail to determine the odds or risk of IBD, Crohn's disease (CD) or ulcerative colitis (UC) amongst individuals with vs without evidence of cagA expression (eg CagA seropositivity). Estimates were pooled using a random effects model.

Results: Three clinical studies met inclusion criteria. cagA expression was represented by CagA seropositivity in all studies. Compared to CagA seronegativity overall, CagA seropositivity was associated with lower odds of IBD (OR 0.31, 95% CI 0.21-0.44) and CD (OR 0.25, 95% CI 0.17-0.38), and statistically nonsignificant lower odds for UC (OR 0.68, 95% CI 0.35-1.32). Similarly, compared to H pylori non-exposed individuals, H pylori exposed, CagA seropositive individuals had lower odds of IBD (OR 0.26, 95% CI 0.16-0.41) and CD (OR 0.23, 95% CI 0.15-0.35), but not UC (OR 0.66, 0.34-1.27). However, there was no significant difference in the odds of IBD, CD or UC between H pylori exposed, CagA seronegative and H pylori non-exposed individuals.

Conclusion: We found evidence for a significant association between CagA seropositive H pylori exposure and reduced odds of IBD, particularly CD, but not for CagA seronegative H pylori exposure. Additional studies are needed to confirm these findings and define underlying mechanisms.
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http://dx.doi.org/10.1111/apt.15306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393806PMC
July 2019

Upper Endoscopy up to 3 Years Prior to a Diagnosis of Gastric Cancer Is Associated With Lower Stage of Disease in a USA Multiethnic Urban Population, a Retrospective Study.

J Prev Med Public Health 2019 May 26;52(3):179-187. Epub 2019 Apr 26.

The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Objectives: In the USA, certain races and ethnicities have a disproportionately higher gastric cancer burden. Selective screening might allow for earlier detection and curative resection. Among a USA-based multiracial and ethnic cohort diagnosed with non-cardia gastric cancer (NCGC), we aimed to identify factors associated with curable stage disease at diagnosis.

Methods: We retrospectively identified endoscopically diagnosed and histologically confirmed cases of NCGC at Mount Sinai Hospital in New York City. Demographic, clinical, endoscopic and histologic factors, as well as grade/stage of NCGC at diagnosis were documented. The primary outcome was the frequency of curable-stage NCGC (stage 0-1a) at diagnosis in patients with versus without an endoscopy negative for malignancy prior to their index exam diagnosing NCGC. Additional factors associated with curable-stage disease at diagnosis were determined.

Results: A total of 103 racially and ethnically diverse patients were included. Nearly 38% of NCGC were stage 0-Ia, 34% stage Ib-III, and 20.3% stage IV at diagnosis. A significantly higher frequency of NCGC was diagnosed in curable stages among patients who had undergone an endoscopy that was negative for malignancy prior to their index endoscopy that diagnosed NCGC, compared to patients without a negative endoscopy prior to their index exam (69.6% vs. 28.6%, p=0.003). A prior negative endoscopy was associated with 94.0% higher likelihood of diagnosing curable-stage NCGC (p=0.003). No other factors analyzed were associated with curable-stage NCGC at diagnosis.

Conclusions: Endoscopic screening and surveillance in select high-risk populations might increase diagnoses of curable-stage NCGC. These findings warrant confirmation in larger, prospective studies.
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http://dx.doi.org/10.3961/jpmph.18.262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549011PMC
May 2019

Increased Incidence and Mortality of Gastric Cancer in Immigrant Populations from High to Low Regions of Incidence: A Systematic Review and Meta-Analysis.

Clin Gastroenterol Hepatol 2020 02 30;18(2):347-359.e5. Epub 2019 May 30.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee; Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

Background & Aims: Gastric cancer is the leading cause of infection-related cancer death and the third-leading cause of cancer death worldwide. The effect of immigration on gastric cancer risk is not well-defined but might be helpful for screening or surveillance endeavors. We performed a systematic review and meta-analysis to define the risk of gastric cancer in immigrants from high-incidence regions to low-incidence regions (including Western Europe, Australia, Brazil, Canada, Israel, and the United States).

Methods: We searched MEDLINE and EMBASE databases, from January 1980 to January 2019, for studies that identified immigrants from high-incidence regions of gastric cancer, provided clear definitions of immigrant and reference populations, and provided sufficient data to calculate gastric cancer incidence and gastric cancer-related mortality. We performed meta-analyses of standardized incidence ratios (SIR) for first-generation immigrants from high- to low-incidence regions, stratified by immigrant generation, sex, and anatomic and histologic subtype, when data were available.

Results: We identified 38 cohort studies that met our inclusion criteria. All 13 studies of 21 distinct populations reported significantly increased SIRs for gastric cancer in first-generation foreign-born immigrants (men SIR range, 1.24-4.50 and women SIR range, 1.27-5.05). The pooled SIR for immigrants with all types of gastric cancer was 1.66 (95% CI, 1.52-1.80) for men and 1.83 (95% CI, 1.69-1.98) for women. Nine studies from 2 high-incidence populations (the former Soviet Union and Japan) reported an increased gastric cancer standardized mortality ratio in first-generation immigrants who migrated to regions of low incidence (former Soviet Union immigrants, 1.44-1.91 for men and 1.40-2.56 for women).

Conclusions: Immigrants from regions with a high incidence of gastric cancer to regions of low incidence maintain a higher risk of gastric cancer and related mortality, based on a comprehensive systematic review and meta-analysis. Assessment of immigrant generation along with other risk factors might help identify high-risk populations for prevention and therapeutic interventions.
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http://dx.doi.org/10.1016/j.cgh.2019.05.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911018PMC
February 2020

Management of Inflammatory Bowel Disease-Associated Dysplasia in the Modern Era.

Gastrointest Endosc Clin N Am 2019 Jul 6;29(3):531-548. Epub 2019 Apr 6.

Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, 1468 Madison Avenue, Annenberg Building, Room 5-12, Box 1069, New York, NY, USA. Electronic address:

This article begins with a brief overview of risk factors for colorectal neoplasia in inflammatory bowel disease to concretize the approach to risk stratification. It then provides an up-to-date review of diagnosis and management of dysplasia in inflammatory bowel disease, which integrates new and emerging data in the field. This is particularly relevant in an era of increased attention to cost- and resource-containment from the health systems vantage point, coupled with a heightened prioritization of patient quality of life and shared decision-making. Also provided is a brief discussion of the status of newer therapeutic techniques, such as endoscopic submucosal dissection.
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http://dx.doi.org/10.1016/j.giec.2019.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354094PMC
July 2019

Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis.

Gut 2019 12 28;68(12):2152-2160. Epub 2019 Mar 28.

Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.

Objective: Eosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical implications of concurrent EoO and IBD diagnoses.

Design: We conducted a prospective cohort analysis using the Truven MarketScan database (2009-2016) to estimate the incidence and prevalence of EoO in patients with Crohn's disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses.

Results: Among 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio [IRR] 5.4, p<0.01; prevalence ratio (PR) 7.8, p<0.01) or UC (IRR 3.5, p<0.01; PR 5.0, p<0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p<0.01; PR 7.6, p<0.01; UC: IRR 3.4, p<0.01; PR 4.9, p<0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p<0.01).

Conclusion: Based on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.
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http://dx.doi.org/10.1136/gutjnl-2018-318074DOI Listing
December 2019