Gastric Xanthoma And Gastric Cancer Risk
Gastric cancer stands as a formidable global threat, ranking among the top cancers in incidence and mortality. Amidst known risk factors like dietary habits and infections, a lesser-known player, gastric xanthoma (GX), emerges as a potential link to this complex puzzle. This study delves into the enigmatic relationship between gastric xanthoma and precancerous gastric lesions, aiming to shed light on this curious association. By analyzing records of patients who underwent upper gastrointestinal endoscopy, the research seeks to unravel the role of gastric xanthoma in the trajectory toward gastric cancer, potentially offering new insights into this pressing public health concern.
THE BACKGROUND OF THE STUDY
The role of gastric cancer in terms of global impact is striking, ranking fifth in incidence and fourth in mortality among all malignancies worldwide in 2020. The most substantial burden falls on Asia, particularly in China, where it ranks as the third most prevalent malignancy, contributing significantly to both new cancer cases and associated deaths annually [1,2]. Gastric cancer’s multifaceted etiology encompasses various factors, including a family history of gastric cancer, dietary habits, smoking, and alcohol consumption, and infections like Helicobacter pylori and Epstein–Barr virus [3-6].
In this complex landscape of risk factors, gastric xanthoma (GX) emerges as a unique benign gastric lesion characterized by the accumulation of fatty deposits within the gastric mucosa, often referred to as “gastric macular tumor” or “gastric lipid island.” GX’s incidence varies, ranging from 0.018% to 7% [7,8]. This benign entity typically presents as single or multiple yellow-white nodules or plaques with a rough surface and distinct boundaries. At the same time, histologically, it features lipid-phagocytic monocytes and macrophages transforming into foam cells that cluster in nests within the mucosa and submucosa [9,10]. Although GX often presents with non-specific clinical features, such as dyspepsia or upper abdominal discomfort, its association with concurrent diseases has raised interest. Recent years have increased GX incidence due to advanced endoscopic techniques and evolving dietary and environmental factors .
Notably, gastric xanthoma has been linked to gastric atrophy and intestinal metaplasia, making it a potential susceptibility factor for the development of gastric cancer in patients with chronic atrophic gastritis. This benign entity is also considered a predictive indicator for gastric cancer [12-14]. Despite the implications, comprehensive studies exploring the relationship between gastric xanthoma and gastric precancerous lesions or gastric cancer are scarce. To address this knowledge gap, a retrospective study was initiated to evaluate and elucidate the association between gastric xanthoma and gastric precancerous lesions and gastric cancer .
The research involves the review of medical records of patients who underwent upper gastrointestinal endoscopy and histological examination between January 2020 and December 2021. The study assesses patients diagnosed with chronic gastritis, intestinal metaplasia, intraepithelial neoplasia, or gastric cancer, excluding those with benign gastric or duodenal ulcers, esophageal or duodenal cancer, nonepithelial stomach tumors, acute upper gastrointestinal tract injuries, and patients who had undergone endoscopic submucosal dissection (ESD), gastrectomy, or radio-chemotherapy. The study was conducted per the Declaration of Helsinki (Brazil, 2013), with patient consent waived due to the retrospective nature of the research .
THE STUDY METHOD
The retrospective study involved a meticulous review of medical records from January 2020 (1/2020) to December 2021 (12/2021) at our institution, focusing on patients who underwent upper gastrointestinal endoscopy and histological examination. Inclusion criteria comprised patients diagnosed with chronic gastritis, intestinal metaplasia, intraepithelial neoplasia, or gastric cancer, ensuring adequate information available for analysis. Exclusion criteria were established to filter out specific conditions, excluding patients diagnosed with benign gastric or duodenal ulcers, esophageal or duodenal cancer, tumors not of epithelial origin in the stomach (e.g., malignant lymphoma, mesenchymal tumor, and sarcoma), acute upper gastrointestinal tract injuries, those who had undergone endoscopic submucosal dissection (ESD) or gastrectomy or received radio-chemotherapy, as well as cases of portal hypertensive gastropathy and those with insufficient data.
Diagnostic Criteria and Patient Grouping
Diagnoses were established based on gastroscopic and histopathological findings scrutinized by two or more specialized endoscopists. Narrow-band imaging (NBI) magnifying endoscopy was employed for certain patients to diagnose intestinal metaplasia. Lesions that remained undiagnosed during endoscopy underwent confirmation through histopathological examination. In particular, intraepithelial neoplasia and gastric cancer were confirmed through histopathology.
Patients were stratified into three distinct groups according to their diagnoses:
- Chronic Gastritis Group: Encompassing patients diagnosed with chronic atrophic gastritis (CAG) and chronic non-chronic atrophic gastritis (CNAG).
- Precancerous Lesion Group: Consisting of patients diagnosed with intestinal metaplasia and intraepithelial neoplasia.
- Gastric Cancer Group: Comprising patients diagnosed with gastric cancer.
Furthermore, a novel scoring system for gastric cancer screening was applied for patients aged 50 years and above, categorizing them according to age: (<50 years) and (≥50 years).
Crucial data, including patients’ age, sex, endoscopic and histopathological findings, assessment of bile reflux, gastric xanthoma location, and presence and quantity of single or multiple gastric xanthoma lesions, were meticulously extracted from their respective medical records.
The methodology outlines the meticulous selection criteria, diagnostic methods, patient grouping, and comprehensive data collection techniques employed in this retrospective study. The investigation adhered to ethical guidelines and classification protocols to ensure a comprehensive analysis of the patient’s conditions and associated factors.
The analysis was conducted utilizing SPSS software version 26.0 (IBM, Armonk, NY, USA) to scrutinize the data. ANOVA was used to evaluate continuous variables represented as mean standard deviation. Categorical variables were depicted as numbers and percentages, and group comparisons were performed via the chi-square test. To conduct a thorough assessment that considered all relevant factors, a multivariate logistic regression model was applied to the multivariate analysis. In this analysis, statistical significance was set at a two-sided P-value of less than 0.05, signifying results deemed statistically significant based on the data analyzed.
– Total Cases: 47,736 cases were included after exclusion criteria were applied.
– Group Distribution: Chronic gastritis (42,758), precancerous lesions (3,672), and gastric cancer (1,306) cases were identified.
Gastric Xanthoma (GX) Detection:
– Overall Prevalence: gastric xanthoma was detected in 2.85% of the patients.
– Types: 62.06% had a single gastric xanthoma, and 37.94% had multiple lesions.
– Distribution: Gastric antrum showed the highest detection rate (52.50%), followed by the body, entire stomach, cardia, and fundus.
– Demographic Associations: Detection rate increased with age (3.95% in patients aged ≥50 years vs 1.64% in <50 years, P<0.001) and was higher in males (3.26%) than females (2.40%, P<0.001).
GX in Different Lesions:
– Detection Rates: Higher in precancerous lesions (8.39%) compared to chronic gastritis (2.29%) and gastric cancer (5.44%, P=0.001).
– Age and Sex Associations: Detection rates increased with age and male sex, progressing from chronic gastritis to precancerous lesions and gastric cancer.
– Stratified Analysis: Among patients under 50 years, there was no significant difference between precancerous lesions and gastric cancer. However, in patients aged 50 and older, a significant difference existed (P<0.01).
– Association with Lesions: Gastric xanthoma was associated with a higher risk of precancerous lesions (OR 3.197, 95% CI 2.791–3.662, P<0.001) and gastric cancer (OR 1.794, 95% CI 1.394–2.309, P<0.001) compared to chronic gastritis.
Clinical Characteristics of GX Patients in Different Lesion Groups:
– Age and Sex Associations: Proportions of patients aged 50 and older and male patients increased with the progression of mucosal lesions.
– Bile Reflux: More common in gastric xanthoma patients with precancerous lesions than in chronic gastritis or gastric cancer groups.
– GX Location: Mainly detected in the gastric antrum across lesion groups, although slightly varied in cardia, fundus, and entire stomach.
In the present study, the research reaffirmed that gastric xanthoma (GX) was notably higher in older individuals, especially among males, and was predominantly detected as single lesions, primarily in the gastric antrum. These findings align with earlier research attributing gastric xanthoma to older age, male predominance, and its location within the stomach (1-3).
Moreover, the global trends in gastric xanthoma incidence showcased varying detection rates across different regions, with indications of an increasing prevalence over time, albeit with regional disparities (4-6).
The pathogenesis of gastric xanthoma remains ambiguous, with proposed hypotheses suggesting an association between abnormal lipid metabolism and the accumulation of lipids in the gastric mucosa, ultimately leading to GX formation. Additionally, studies have explored connections between GX and various factors, including H. pylori infection, chronic inflammation, cholestasis, and immunosuppression (7-10).
Furthermore, the research indicates a potential association between GX and the development of gastric cancer and precancerous lesions. The study confirms higher gastric xanthoma prevalence in the precancerous lesion and gastric cancer groups compared to those diagnosed with chronic gastritis. Multivariate analysis reiterates GX as an independent risk factor for these conditions (11, 12).
GX might resolve spontaneously, implying an early warning sign for precancerous lesions. It underlines the significance of endoscopic follow-up and its potential as an early diagnostic indicator (13).
The study’s discoveries add to the existing knowledge about gastric xanthoma, emphasizing the importance of future large-scale, multi-center prospective studies for a more comprehensive understanding of its link to gastric cancer and precancerous lesions. These investigations will be pivotal in developing preventative measures and early diagnostic indicators for gastric cancer.
LIMITATIONS OF THE STUDY
- Retrospective Nature:
– Incomplete clinical data due to the retrospective study design.
– Lack of comprehensive information on Helicobacter pylori infection, lifestyle, and genetic backgrounds of the participants.
- Limited Imaging:
-The absence of complete endoscopic imaging of the whole stomach may have led to missed lesions, potentially lowering the detection rate.
- Single-Center Study:
– Restricted to a single geographical location with specific dietary structures, thereby limiting the generalizability of the findings.
- Potential Bias from Diagnostic Techniques:
– Use of NBI magnifying endoscopy may have introduced bias in distinguishing between chronic gastritis and intestinal metaplasia, impacting the accuracy of diagnosis.
- Need for More Comprehensive Studies:
– Emphasis on the necessity for large-scale, multi-center prospective studies to explore the causal relationship between gastric xanthoma (GX) and gastric cancer, along with precancerous lesions, for a more comprehensive understanding and better preventive strategies.
These limitations underscore the need for more extensive, varied, and prospective research to gain a clearer understanding of the association between GX and gastric malignancies.
The research findings revealed a substantial correlation between gastric xanthoma (GX) and both gastric cancer and precancerous lesions, underscoring the necessity for further investigation. Currently engaged in a large-scale, multi-centered prospective study, the team aims to establish gastric xanthoma as an independent risk factor for these conditions. It underscores the importance of physicians remaining vigilant with GX-diagnosed patients, closely monitoring for mucosal changes and potential precancerous lesions during endoscopic examinations. Such a comprehensive approach, even in the absence of evident gastric cancer, holds pivotal value for early intervention and preventive strategies against gastric malignancies.
- Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLO-BOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries Cancer J Clin.2021;71(3):209-249. https://pubmed.ncbi.nlm.nih.gov/33538338/
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- Lynch HT, Grady W, Suriano G, Huntsman D. Gastric cancer: new genetic developments.J Surg Oncol. 2005;90(3):114-133. https://pubmed.ncbi.nlm.nih.gov/15895459/
- Kim J, Cho YA, Choi WJ, Jeong SH. Gene–diet interactions in gastric cancer risk: a systematic review.World J Gastroenterol. 2014;20(28):9600-9610. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110595/
- Moy KA, Fan YH, Wang RW, Gao YT, Yu MC, Yuan JM. Alcohol and tobacco use in relation to gastric cancer: a prospective study of men in Shanghai, China.Cancer Epidemiol Biomarkers Prev. 2010;19(9):2287-2297. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936659/
- Iizasa H, Nanbo A, Nishikawa J, Jinushi M, Yoshiyama H. Epstein–Barr Virus (EBV)-associated gastric carcinoma.Viruses. 2012;4(12):3420-3439. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528272/
- Petrov S, Churtchev J, Mitova R, Boyanova L, Tarassov M. Xanthoma of the stomach–some morphometrical peculiarities and scanning electron microscopy.Hepatogastroenterology.1999;46(26):1220-1222. https://pubmed.ncbi.nlm.nih.gov/10370695/
- Yi SY. Dyslipidemia and H. pylori gastric xanthomatosis.World J Gastroenterol.2007;13(34):4598-4601. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611834/
- Oviedo J, Swan N, Farraye FA. Gastric xanthomas.Am J Gastroenterol.2001;96(11):3216-3218. https://pubmed.ncbi.nlm.nih.gov/11721787/
- Kaiserling E, Heinle H, Itabe H, Takano T, Remmele W. Lipid islands in human gastric mucosa: morphological and immunohistochemical findings.Gastroenterology.1996;110(2):369-374. https://pubmed.ncbi.nlm.nih.gov/8566582/
- Deng GZ, Fan ZL, Yang L, Zhang DS, Wang RF, Chen SB. Clinical characteristics analysis on 354 cases of gastric xanthelasma.ContemporaryMed.2019;25(20):80-83. [in Chinese]. https://onlinelibrary.wiley.com/doi/full/10.1111/1751-2980.13202
- Xiao DH, Tong X, Yuan XQ, Wu YL, Chen P. Gastric xanthelasma may be a warning sign of intestinal metaplasia: a cross-sectional study. Oncol Rep. 2020;44(3):1275-1281. https://pubmed.ncbi.nlm.nih.gov/32583002/
- Köksal AŞ, Suna N, Kalkan_IH, et al. Is gastric xanthelasma an alarming endoscopic marker for advanced atrophic gastritis and intestinal metaplasia? Dig Dis Sci. 2016;61(10):2949-2955. https://pubmed.ncbi.nlm.nih.gov/27250981/
- Sekikawa A, Fukui H, Sada R, et al. Gastric atrophy and xanthelasma are markers for predicting the development of early gastric cancer. J Gastroenterol. 2016;51(1):35-42. https://pubmed.ncbi.nlm.nih.gov/25904098/
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