Premalignant Gastric Lesions Research Articles

A Summary of the 2020 Gastric Cancer Summit at Stanford University

There exists no coherent national strategy for the early detection or prevention of gastric cancer in the United States (US), even among identified high-risk groups such as Asian Americans, African Americans, Hispanic Americans, and Alaska Native/American Indian peoples. As a result, patients with gastric cancer in the US are diagnosed at later stages and demonstrate worse overall survival compared to nations of East Asia with established screening programs (Table 1). The under-recognition of gastric cancer risk within minority communities is a significant unaddressed healthcare disparity.

1-Year Follow-up of Single Anastomosis Sleeve Ileal (SASI) Bypass in Morbid Obese Patients: Efficacy and Concerns.

Single anastomosis sleeve ileal (SASI) bypass is a new bariatric and metabolic procedure that has both restrictive and malabsorptive effects. This study was conducted to assess both the efficacy and safety of this procedure in a short-term follow-up. This retrospective cohort study examined weight loss- and obesity-related comorbidities and complications in patients who had undergone SASI bypass from October 2017 to March 2018 at a center of excellence for bariatric/metabolic surgery. Twenty-four patients had undergone SASI bypass due to some existing risk factors of gastric cancer or premalignant lesions in the esophagogastroduodenoscopy. The mean BMI of the patients was 44.2 (median 43.7, range 37.0-54.8) kg/m2. Six and 12months after surgery, the mean (median) excessive weight loss (EWL) was 67.8% (63.3) and 86.2% (82.9) and total weight loss (TWL) was 28.5% (27.6) and 36.46% (35.8), respectively. Most patients had complete remission in type 2 diabetes mellitus (89%), arterial hypertension (86%), dyslipidemia (100%), obstructive sleep apnea (100%), and non-alcoholic fatty liver disease (73%) during the 1year after surgery. One case of extra-luminal bleeding and one case of trocar site hernia occurred after surgery. Moreover, two patients converted to sleeve gastrectomy because of hypoalbuminemia and EWL about 1year after SASI. SASI bypass is a newly introduced investigational procedure for improving weight loss and comorbidities; however, it may result in EWL and protein malnutrition and should only be performed for select patients and by well-experienced bariatric surgeons.

Abstract PR03: An integrative mouse model of gastric premalignancy that combines early genomic alterations with disease-relevant carcinogenic exposure

Abstract Carcinogenesis from dietary byproducts and inflammation is the strongest risk factor for gastric cancer, which carries a poor prognosis owing to its advanced stage at the time of diagnosis. We therefore have a critical need to characterize key molecular mechanisms of carcinogenesis at the earliest conception of this ominous disease. To this end, we designed an integrative mouse model that combines two essential contributors to the premalignant state: (1) disease-relevant carcinogenic exposure and (2) an early genomic alteration. We recently discovered that, contrary to the previously accepted paradigm, TP53 is mutated early in malignant progression, often occurring before dysplasia. Based on these findings, we adapted a transgenic mouse to conditionally delete Trp53 in the Lgr5+ stem cell compartment of the stomach, and then exposed these mice to drinking water containing the bile acid deoxycholate (DCA), a principal component of gastroduodenal reflux, and nitroso-compound MNU, a disease-relevant carcinogen. Deletion of Trp53 in gastric stem cells of untreated mice did not lead to detectable premalignant lesions. By contrast, inactivation of Trp53in Lgr5+ stem cells of DCA/MNU-treated mice led to a 3.5-fold increase in premalignant lesions compared to wild-type control mice after one year. Whole-exome sequencing of gastric lesions showed a mutational signature associated with MNU exposure, validating that carcinogenesis contributed to the emergence of premalignant gastric lesions. Three-dimensional organoid culture recapitulates epithelial cell orientation, differentiation, and behavior in vitro. To characterize and functionally study the epithelial compartment of premalignant lesions, gastric organoids were generated from the integrative mouse model, capturing critical intermediate states in the evolution of gastric premalignancy such as genome doubling. Unbiased gene expression analyses revealed that inactivation of Trp53 in gastric premalignancy leads to activation of interferon, WNT/stemness, and cell cycle checkpoint pathways. CDKN2A was the most notable cell cycle regulator induced by Trp53 loss, which prevented progression of disease and ultimately endowed a selective pressure for inactivation in route to cancer. Indeed, genomic analysis of patient data revealed that CDKN2A and TP53 are significantly coaltered in human gastric cancer. These data demonstrate that integrating early genomic events with disease-relevant carcinogenic exposure can generate a more faithful mouse model of the premalignant state than could be achieved by either method alone. By defining the precise molecular mediators that collaborate with carcinogenesis to endorse premalignant gastric lesions, we hope to inform the design of effective prevention strategies tailored to definitively treat patients before a window of opportunity has closed. This abstract is also being presented as Poster A37. Citation Format: Nilay Sethi, Osamu Kikuchi, Gina Duronio, Matthew Stachler, James McFarland, Adam J. Bass. An integrative mouse model of gastric premalignancy that combines early genomic alterations with disease-relevant carcinogenic exposure [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr PR03.

Abstract IA06: Understanding the molecular landscape of gastric premalignant lesions

Abstract Even though the incidence of gastric cancer has been declining over the years, it still has a very high mortality rate. The incidence and mortality of gastric cancer is, however, significantly higher in minority populations with African Americans and Hispanic individuals presenting 52% and 43%, respectively, more cases than Caucasians (data for male patients). Gastric adenocarcinoma has been strongly associated to infection with Helicobacter pylori (H. pylori). The infection triggers an inflammatory cascade, known as the Correa's cascade, that changes the normal gastric epithelium into nonatrophic gastritis (NAG), multifocal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia, and cancer. It is known that these events involve immune infiltration and damage to the gastric mucosa; however, there is still too much to learn about the gastric premalignant stages and the evolution of them over time. Over the years we have identified single-nucleotide polymorphisms (SNPs) and differential expression of genes associated with premalignant stages and with evolution of the disease over time. We found that African Americans have increased incidence of advanced premalignant lesions and have more prevalence of infection with H. pylori than Whites. In addition, we found that SNPs and haplotypes in the interleukin 1 b gene (IL1B) are associated with advanced gastritis in African American individuals. Interestingly, the frequency of these inflammatory SNPs and haplotypes is different among African American and Caucasian individuals. In terms of gene expression, we have also found that the increased expression of the gene deleted in malignant brain tumors 1 (DMBT1) is associated with the development of advanced gastritis while the expression of CD44 is associated with progression of the disease over time. Given that CD44 is a molecule involved in the homing of inflammatory cells, its association with progression of premalignant stages over time highlights the role of the immune response in the outcome of these lesions. Interestingly, these immune responses seem to be also modulated by H. pylori itself. We have shown that H. pylori components are able to modulate acquired and innate immune responses. In addition, we have also found a microRNA pattern associated with advanced premalignant gastric lesions in both African Americans and Caucasians. Understanding the molecular landscape of the gastric lesions may help us devise strategies to intervene and limit their progression into more advanced lesions, including gastric cancer. Citation Format: Jone Garai, Maria B. Piazuelo, Maria C. Camargo, Pelayo Correa, Keith Wilson, Jovanny Zabaleta. Understanding the molecular landscape of gastric premalignant lesions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA06.

Contrasting serum biomarker profiles in two Colombian populations with different risks for progression of premalignant gastric lesions during chronic Helicobacter pylori infection

BackgroundColombians in coastal Tumaco have a lower incidence of Helicobacter pylori-associated gastric cancer compared to individuals from Tuquerres in the high Andes. This is despite nearly universal prevalence of H. pylori infection and chronic gastritis. MethodsH. pylori infection was confirmed by Steiner stain and serology using African and European-origin strains. Gastric histology and serum inflammatory biomarkers in dyspeptic Tumaco or Tuquerres patients were evaluated to predict progression of gastric lesions. ResultsH. pylori infection was nearly universal by Steiner stain and serology. IgG response to European-origin H. pylori strains were greater than African-origin. High gastric cancer-risk Tuquerres patients, compared to low-risk Tumaco, had significant odds ratios for lesion progression associated with serum IL-5, trefoil factor 3 (TFF3), and low pepsinogen I/II ratio. Sensitivity and specificity for these parameters was 63.8% and 67.9%, respectively, with correctly classifying patients at 66.7%. Most odds ratios for 26 other biomarkers were significant for the town of residency, indicating an environmental impact on Tumaco patients associated with decreased lesion progression. ConclusionAn IL-5 association with progression of gastric lesions is novel and could be evaluated in addition to TFF3 and pepsinogen I/II ratio as a non-invasive prognostic screen. Results suggest Tumaco patients were exposed to infectious diseases beyond H. pylori such as the documented high incidence of helminthiasis and toxoplasmosis. ImpactResults support a prior recommendation to evaluate TFF3 and pepsinogen I/II together to predict aggressive gastric histology. Our data indicate IL-5 should be further evaluated as prognostic parameter.

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high-grade premalignant gastric lesions.

Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.

Molecular profiling of gastric cancer in a population with high HIV prevalence reveals a shift to MLH1 loss but not the EBV subtype.

The human immunodeficiency virus (HIV) pandemic heavily affects sub‐Saharan Africa. It is associated with persistently active Epstein‐Barr virus (EBV) infection. To determine if this translates into increased frequency of EBV‐associated gastric cancer (EBVaGC), we evaluated molecular profiles of gastric cancer (GC) in Zambia. Patients with GC or premalignant gastric lesions were enrolled in Lusaka, Zambia. We used patients without any of these lesions as a control group. Chromogenic in situ hybridization (CISH) on tumor tissue was used to identify EBVaGC. To identify the microsatellite unstable subtype, immunofluorescence staining for MutL homolog 1 (MLH1) was used. Exposure to EBV and HIV was assessed serologically. We enrolled 369 patients (median age 52 years [IQR 41‐65]; 198 (54%) female). Of these, 72 (20%) had GC and 35 (9%) had gastric premalignant lesions (PL). CISH identified EBVaGC in 5/44 (11%) of those with adequate tissue, while MLH1 loss was identified in 29/45 (64%). Both GC and PL were associated with the highest titers of antibodies to Early antigen‐diffuse (OR 2.5, 95% CI 1.0‐6.1, P = .048 and OR 3.9, 95% CI 1.1‐12.9, P = .03, respectively) at high concentrations. Human immunodeficiency virus infection was associated with a range of antibodies to EBV, but not with any cancer subtype. Despite the association of HIV with persistent EBV, the proportion of EBVaGC in Zambia is similar to populations with a low prevalence of HIV infection. The proportion of microsatellite unstable tumors may be higher than other populations.

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression.

The extracellular matrix (ECM) is a dynamic and highly organized tissue structure, providing support and maintaining normal epithelial architecture. In the last decade, increasing evidence has emerged demonstrating that alterations in ECM composition and assembly strongly affect cellular function and behavior. Even though the detailed mechanisms underlying cell-ECM crosstalk are yet to unravel, it is well established that ECM deregulation accompanies the development of many pathological conditions, such as gastric cancer. Notably, gastric cancer remains a worldwide concern, representing the third most frequent cause of cancer-associated deaths. Despite increased surveillance protocols, patients are usually diagnosed at advanced disease stages, urging the identification of novel diagnostic biomarkers and efficient therapeutic strategies. In this review, we provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive biomarkers of the disease or as potential targets in gastric cancer.

Gastric precancerous lesions present in ApcMin/+ mice

The ApcMin/+ mouse is an animal model for familial adenomatous polyposis, and aged ApcMin/+ mice also spontaneously develop multiple tumors in their stomachs. However, gastric premalignant lesions in ApcMin/+ mice have not been well characterized. The stomachs of ApcMin/+ mice were compared with those of their wild type littermates at 24 weeks with hematoxylin and eosin (H&E) staining and alcian blue staining. Ki67, CD68 and CA199 expression was analyzed by immunohistochemistry. The results revealed the presence of epithelial proliferation and inflammatory infiltration in the forestomachs, glandular atrophy and intestinal metaplasia in the gastric bodies, and dysplasia in the gastric antra. The effect of mutations in the Apc gene on chronic gastritis and gastric precancerous lesions was characterized in ApcMin/+ mice. These results suggest that ApcMin/+ mice represent a genetic model for mechanistic studies and drug discovery in gastric precancerous lesions.

Gastric Histopathologic Findings in South Italian Morbidly Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy: Is Histopathologic Examination of All Resected Gastric Specimens Necessary?

The value of the routine histopathologic examination of resected gastric remnants following laparoscopic sleeve gastrectomy (LSG) remains to be controversial. This study aimed to determine whether the routine histopathologic examination of gastric specimens is necessary for all patients undergoing LSG if upper gastrointestinal endoscopy (UGIE) plus multiple biopsies are performed routinely during the preoperative work-up. Clinicopathologic data of 474 patients who underwent LSG were analysed. Types of histopathologic findings in LSG specimens and the prevalence of these and Helicobacter pylori (HP) infection were estimated. Comparisons were conducted to assess the association of risk factors with the most frequent abnormal and premalignant histopathologic findings. Chronic gastritis was the most common gastric pathology (63.5%) and premalignant lesions were present in 7.8% of the specimens. The prevalence of HP infection was 36.9%. A statistically significant association was observed between HP infection and chronic gastritis (P = .000), and premalignant lesions (P = .000). Similarly, a statistically significant association was noted between age and premalignant gastric lesions (P = .000). Histopathologic examination of LSG specimens may not be routinely needed and can be performed on selected patients. While we recommend routine preoperative UGIE in all LSG-treated patients, we suggest that histopathologic assessment of the LSG specimens should be mandatory when UGIE biopsies demonstrate HP infection and/or premalignant lesions, in all patients older than 42 years, and in cases of intraoperative detection of incidental tumours or suspicious lesions.

Prevalence, Characteristics and Endoscopic Management of Gastric Premalignant Lesions in France

Introduction: Surveillance of gastric precancerous lesions (GPL) is recommended, but the data on their clinical and endoscopic management in a “real-life” practice are limited. Our aim was to study the modalities of endoscopic management of patients with GPL in France. Design: All the patients diagnosed with GPL in our center between 2000 and 2015 were grouped and analyzed according to the most severe GPL found, in the following order: atrophic gastritis only (AG), intestinal metaplasia (IM), low grade dysplasia (LGD), high grade dysplasia (HGD). Results: Out of 16,764 patients having undergone upper endoscopy with gastric biopsies, 507 were identified with GPL (detection rate 3.2%). Overall, Helicobacter pylori infection was found in 41% of patients. IM was by far the most frequently found lesion (79%), followed by LGD (17%), HGD (2%), and AG only (2%). H. pylori infection rate was decreasing, while the age of the patients was increasing, together with the increasing severity of GPL (p = 0.005). Only 28% of the patients had at least one follow-up endoscopy. No correlation was found between the endoscopist’s appreciation of the mucosa and histological results. Conclusion: In France, GPL can be expected in about 3% of patients undergoing upper endoscopy with gastric biopsies for any reason. The correlation between the endoscopic evaluation and histology is poor. Spreading of published guidelines should improve the management of patients with GPL in the future.

Biopsy strategies for endoscopic screening of pre-malignant gastric lesions

Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) were adopted to evaluate gastric risk stratification in five biopsy samples. This study aimed to evaluate the degree of gastric atrophy (GA) and intestinal metaplasia (IM) in five locations to detect a more representative biopsy sample in gastric cancer (GC) screening. Our study enrolled 368 patients and 5 biopsy pieces were acquired from them. Gastric risk stratification was calculated by OLGA and OLGIM staging system. The results revealed that the IM score in the incisura angularis was higher than that in the larger and lesser curvature of corpus mucosa (p = 0.037 and p = 0.030, respectively) and the IM score in the lesser curvature of antrum mucosa was higher than that in the incisura angularis mucosa (p = 0.018). IM is more frequently observed in the angulus region than in the lesser curvature of corpus in the mild degree (p = 0.004) and mild IM lesions in the lesser curvature of antrum were more frequently observed than in the incisura angularis mucosa (p = 0.004), Four biopsy pieces protocol (larger curvature and lesser curvature of the antrum, lesser curvature of the corpus and angulus) demonstrated accurate consistency (97.83% and 98.37%, respectively) with a Kendall’s tau-b of higher than 0.990, along with low misdiagnosis rates of OLGA and OLGIM (III + IV) (9.76% and 5.00%, respectively). Three biopsy pieces protocol (lesser curvature of the antrum and corpus, angulus biopsy) in OLGA and OLGIM staging system was close to the standard protocol (five biopsy specimens) with a consistency of 94.84% and 94.29% and has a Kendall’s tau-b higher than 0.950 and diagnostic omission rates of 9.76% and 5.00%, respectively, which was exactly the same with the four biopsy pieces protocol. Furthermore, it had the second-highest Youden index (0.902 and 0.950, respectively) and area under the ROC curve (0.992 and 0.996, respectively) for the screening of high-risk GC by OLGA and OLGIM stages. Thus, we recommended the angulus and the lesser curvature of antrum as a conventional biopsy and three biopsy pieces for further GC risk screening.

Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions.

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.

Gastro-duodenal disease in Africa: Literature review and clinical data from Accra, Ghana.

Gastroduodenal disease (GDD) was initially thought to be uncommon in Africa. Amongst others, lack of access to optimal health infrastructure and suspicion of conventional medicine resulted in the reported prevalence of GDD being significantly lower than that in other areas of the world. Following the increasing availability of flexible upper gastro-intestinal endoscopy, it has now become apparent that GDD, especially peptic ulcer disease (PUD), is prevalent across the continent of Africa. Recognised risk factors for gastric cancer (GCA) include Helicobater pylori (H. pylori), diet, Epstein-Barr virus infection and industrial chemical exposure, while those for PUD are H. pylori, non-steroidal anti-inflammatory drug (NSAID)-use, smoking and alcohol consumption. Of these, H. pylori is generally accepted to be causally related to the development of atrophic gastritis (AG), intestinal metaplasia (IM), PUD and distal GCA. Here, we perform a systematic review of the patterns of GDD across Africa obtained with endoscopy, and complement the analysis with new data obtained on pre-malignant gastric his-topathological lesions in Accra, Ghana which was compared with previous data from Maputo, Mozambique. As there is a general lack of structured cohort studies in Africa, we also considered endoscopy-based hospital or tertiary centre studies of symptomatic individuals. In Africa, there is considerable heterogeneity in the prevalence of PUD with no clear geographical patterns. Furthermore, there are differences in PUD within-country despite universally endemic H. pylori infection. PUD is not uncommon in Africa. Most of the African tertiary-centre studies had higher prevalence of PUD when compared with similar studies in western countries. An additional intriguing observation is a recent, ongoing decline in PUD in some African countries where H. pylori infection is still high. One possible reason for the high, sustained prevalence of PUD may be the significant use of NSAIDs in local or over-the-counter preparations. The prevalence of AG and IM, were similar or modestly higher over rates in western countries but lower than those seen in Asia. . In our new data, sampling of 136 patients in Accra detected evidence of pre-malignant lesions (AG and/or IM) in 20 individuals (14.7%). Likewise, the prevalence of pre-malignant lesions, in a sample of 109 patients from Maputo, were 8.3% AG and 8.3% IM. While H. pylori is endemic in Africa, the observed prevalence for GCA is rather low. However, cancer data is drawn from country cancer registries that are not comprehensive due to considerable variation in the availability of efficient local cancer reporting systems, diagnostic health facilities and expertise. Validation of cases and their source as well as specificity of outcome definitions are not explicit in most studies further contributing to uncertainty about the precise incidence rates of GCA on the continent. We conclude that evidence is still lacking to support (or not) the African enigma theory due to inconsistencies in the data that indicate a particularly low incidence of GDD in African countries.

Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

Intestinal-type gastric cancer is preceded by premalignant lesions, including chronic atrophic gastritis and intestinal metaplasia. In this study, we constructed a single-cell atlas for 32,332 high-quality cells from gastric antral mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing. We then constructed a single-cell network underlying cellular and molecular characteristics of gastric epithelial cells across different lesions. We found that gland mucous cells tended to acquire an intestinal-like stem cell phenotype during metaplasia, and we identified OR51E1 as a marker for unique endocrine cells in the early-malignant lesion. We also found that HES6 might mark the pre-goblet cell cluster, potentially aiding identification of metaplasia at the early stage. Finally, we identified a panel of EGC-specific signatures, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions.

Su1263 – Assessment of Gastric Premalignant Lesions by Anatomic Subsite in Individuals Who Subsequently Developed Helicobacter Pylori-Associated Gastric Cancer in a High-Risk Colombian Cohort

Su1263 – Assessment of Gastric Premalignant Lesions by Anatomic Subsite in Individuals Who Subsequently Developed Helicobacter Pylori-Associated Gastric Cancer in a High-Risk Colombian Cohort

Prevalence and determinants of serological evidence of atrophic gastritis among Arab and Jewish residents of Jerusalem: a cross-sectional study

ObjectiveUnderstanding the correlates of premalignant gastric lesions is essential for gastric cancer prevention. We examined the prevalence and correlates of serological evidence of atrophic gastritis, a premalignant gastric condition, using...

Label-Free Assessment of Premalignant Gastric Lesions Using Multimodal Nonlinear Optical Microscopy

In this paper, a nonlinear optical microscopy employing two-photon excited fluorescence and second-harmonic generation was used for the detection of premalignant gastric lesions. It was found that gland morphology and collagen structure in mucosa will change with the progression of gastric diseases from normal to intestinal metaplasia, to low-grade intraepithelial neoplasia, and to high-grade intraepithelial neoplasia, and this microscopy was able to directly distinguish these warning symptoms. Furthermore, two features were quantified from nonlinear optical images to demonstrate the changes of gland size and collagen content during the development process of preneoplastic lesions. These results clearly show that nonlinear optical microscopy can effectively differentiate normal and precancerous gastric tissues without contrast agents, which would be helpful for early diagnosis and treatment of gastric diseases. This study may provide the groundwork for further application of nonlinear optical microscopy in clinical practice.

The CAT-262 C>T, MnSOD Ala16Val, GPX1 Pro198Leu Polymorphisms Related to Oxidative Stress and the Presence of Gastric Lesions.

The increased oxidative stress plays an important role in gastro-duodenal ulcers and gastric cancer occurrence. We investigated the association between the genetic polymorphisms of genes encoding the antioxidative enzymes CAT, GPX and SOD and the occurrence of gastric lesions, considering also the environmental risk factors such as H. pylori infection, drug exposure, smoking and alcohol consumption. We included 373 patients who underwent endoscopy for symptoms, anemia or bleeding investigation. A complete set of demographical, clinical and pathological data was recorded. All patients were successfully genotyped. In the multivariate logistic regression model, the patients having Pro/Pro genotype of GPX1 gene polymorphism had more severe gastric lesions as compared with patients with the Leu/Pro or Leu/Leu genotype (OR= 1.89, 95%CI: 0.99-3.57, p=0.051). The GPX1 Pro198Leu and the MnSOD Ala16Val gene polymorphism could be independent risk factors for reactive gastropathy changes, as shown by their association very close to statistical significance (p=0.059 and p=0.054, respectively). Consumption of anticoagulants was a significant independent predictor (p=0.023, OR:0.43 95%CI:0.21-0.89) for the absence of active gastritis, while low-dose aspirin consumption was a risk factor for active gastritis in biopsy samples (p=0.025, OR:1.71, 95%CI:1.07-2.74). The variant genotype of GPX1Pro198Leu was associated with an increased risk for reactive gastropathy changes in gastric biopsies and with less severe endoscopic lesions, while MnSODAla16Val variant genotype (Val/Val or Val/Ala) seems to be related to the reactive gastropathy. However, none of them were associated with inflammatory or premalignant gastric lesions.

Chronic Statin Therapy and Histologic Gastric Changes

Abstract Background: The additional benefits of certain frequently used chronic drugs such as statins or aspirin are investigated for their possible effect of influencing various types of cancer, including gastric cancer. The possible role of statins in the occurrence of pre-neoplastic gastric lesions has not been investigated. Aim: The study aims to determine the influence of chronic statin therapy on premalignant gastric lesions (glandular atrophy, intestinal metaplasia and dysplasia), adjusted with the most important aggressive environmental factors of the gastric mucosa (Helicobacter pylori [H. pylori] infection, low-dose aspirin [acetylsalicylic acid, ASA], biliary reflux, smoking, alcohol consumption). Method: The study included 566 patients with cardiovascular diseases who underwent an upper endoscopy: 222 patients with chronic statin therapy (atorvastatin 20–80 mg/day or rosuvastatin 5–20 mg/day for at least 6 months) and 344 patients without statin intake. A complete set of biopsies from the gastric antrum and corpus were routinely processed and examined, and demographical, clinical, and pathological variables were recorded. Results: Active H. pylori infection in gastric biopsies (p = 0.45), biliary reflux (p = 0.74), alcohol consumption (p = 0.43), or prior ulcer disease (p = 0.07; OR: 0.59; 95% CI: 0.33–1.04) were not associated with an increased risk for premalignant lesions, neither in the statin, nor the no-statin group. Smoking was associated with premalignant lesions in both groups (p = 0.01; OR: 2.24; 95% CI: 1.12–4.47; and p = 0.04; OR: 1.72; 95% CI: 1.01–2.94, respectively), while chronic use of ASA had no influence (p = 0.24, respective p = 0.35). In multivariate regression models, chronic treatment with statins had a protective effect (p = 0.006; OR: 0.59; 95% CI: 0.4–0.8), while smoking (p = 0.01; OR: 1.99; 95% CI: 1.17–3.39) and age >50 years (p <0.01, OR: 3.09; 95% CI: 1.84–5.21) were predictors for pre-neoplastic lesions. H. pylori infection, gender, alcohol consumption, biliary reflux, or prior ulcer disease were not associated with premalignant lesions (p >0.05). Conclusions: In the studied population, chronic statin treatment seems to be associated with a decreased risk for premalignant gastric lesions, while age over 50 years and smoking, regardless of gender or ASA consumption, remain the most important risk factors for premalignant gastric lesions.