Introduction

Gastric cancer is the second leading cause of cancer-related deaths worldwide.¹ High-density lipoprotein cholesterol (HDL-C) reduces cardiovascular disease and related mortality. Moreover, HDL-C has been reported to contribute to the development and prognosis of several cancers.^2-4 However, studies on the effects of HDL-C on gastric cancer mortality are few, and the results are inconsistent.

Aims & Methods

In this study, we investigated the effects of HDL-C on gastric cancer mortality and conducted sub-group analysis by sex and treatment modality. We used data from the National Health Insurance Service System (NHISS) to investigate the effects of HDL-C levels on mortality in patients with gastric cancer. Newly diagnosed patients with gastric cancer (n=22,468) who underwent gastric cancer screening between January 2011 and December 2013 were included and followed-up until 2018. We validated our main results using data from a university hospital cohort. A validation cohort (n=3,379) that had newly diagnosed gastric cancer from 2005 to 2013 at a university hospital, was followed up until 2017. Furthermore, we analyzed the effects of HDL-C levels according to sex and treatment modality (endoscopic resection and gastrectomy).

Results

HDL-C was inversely related with mortality; adjusted hazard ratio (aHR) 0.90 (95% confidence interval [CI], 0.83–0.98) for HDL-C of 40–49 mg/dL, 0.86 (0.79–0.93) for HDL-C of 50–59 mg/dL, 0.82 (0.74–0.90) for HDL-C of 60–69 mg/dL, and 0.78 (0.69–0.87) for HDL-C ≥ 70 mg/dL compared to HDL-C < 40 mg/dL. In the validation cohort, HDL-C was also inversely associated with mortality; aHR 0.81 (0.65–0.99) for HDL-C of 40–49 mg/dL, 0.64 (0.50–0.82) for HDL-C of 50–59 mg/dL, and 0.46 (0.34–0.62) for HDL-C ≥ 60 mg/dL compared to HDL-C < 40 mg/dL. The two cohorts demonstrated consistent favorable effects of higher HDL-C on mortality in both sexes. In validation cohort, the beneficial effect of HDL-C was observed in both gastrectomy and endoscopic resection (P for trend <0.001) with more remarkable in endoscopic resection group.

Conclusion

In this study, we explored that an increased HDL-C reduced mortality in both sexes and curative resection group. Hence, HDL-C could be considered in the prognosis of gastric cancer.

References

1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021, 71, 209–249.
2. Katzke, V.A.; Sookthai, D.; Johnson, T.; Kühn, T.; Kaaks, R. Blood lipids and lipoproteins in relation to incidence and mortality risks for CVD and cancer in the prospective EPIC-Heidelberg cohort. BMC Med. 2017, 15, 218.
3. Cedó, L.; Reddy, S.T.; Mato, E.; Blanco-Vaca, F.; Escolà-Gil, J.C. HDL and LDL: Potential New Players in Breast Cancer Development. J Clin Med. 2019, 8.
4. Nam, S.Y.; Park, B.J.; Nam, J.H.; Kook, M.C. Effect of Helicobacter pylori eradication and high-density lipoprotein on the risk of de novo gastric cancer development. Gastrointest Endosc. 2019, 90, 448-456.e1.

Introduction

Gastric cancer remains one of the leading causes of death internationally and a major health concern in the United States (US). To develop better prevention strategies, this study quantifies trends in gastric cancer related mortality, stratified by age, sex, region, urbanity, and race over two decades.

Aims & Methods

Our study used the CDC WONDER database to analyze death certificates from 1999 to 2022 across the U.S. ICD codes C16.0-C16.9 were used to identify the relevant cases. Demographic variables such as sex, race, age, urban-rural classification, and census regions were analyzed. Trends in AAMR were assessed using the Joint Point Regression Program to determine annual percentage changes (APC).

Results

Overall mortality related to malignant stomach neoplasms in the US declined significantly (Table 1) from 79.26 (1999) to 44.81 (2022), with notable periods of steep decrease between 1999–2006 (APC -3.51, 95% CI: -5.16 to -2.78) and 2006–2018 (APC -2.27, 95% CI: -3.55 to -1.83). Men consistently exhibited higher mortality rates than women (overall men: 81.14 vs women: 42.10). Men experienced an initial significant drop from 113.45 to 78.68 (1999–2009, APC -3.55), followed by a slower decrease till 2022 (APC -2.22). Women's mortality showed an initial sharp decline (1999–2008, APC -3.11), then a modest reduction from 2008–2018 (APC -1.96), plateauing thereafter.

Racially, Non-Hispanic (NH) Black individuals exhibited the highest mortality (109.37), followed by NH Asians/Pacific Islanders (102.47), Hispanic/Latino (91.93), NH American Indian/Alaskan Natives (78.21), and NH White (44.85). NH Blacks demonstrated a marked initial decrease (159.46 to 119.13 by 2017) then plateaued. NH Whites showed a continuous decline (1999–2018), slowing post-2018. Hispanics had two significant declining periods (1999–2011, APC -2.82; 2011–2022, APC -1.56), whereas NH Asians and NH American Indians steadily declined throughout.

Mortality by age was highest among older adults (202.46), followed by middle-aged (60.58) and young adults (40.55). Older adults had two notable decreasing phases (1999–2009, APC -3.56; 2009–2018, APC -2.89), with slower decline afterward. Middle-aged adults showed an initial steep decline (1999–2005, APC -3.65), followed by gradual reduction (2005–2022, APC -0.79). Young adults exhibited minimal, non-significant declines throughout.

Regionally, the Northeast showed highest mortality (64.78), followed by West, South, and Midwest. Both metropolitan and non-metropolitan areas saw significant mortality reductions, with non-metropolitan areas consistently having higher rates overall.

Table 1. Annual Percent Change (APC) in mortality rates by selected demographics, 1999–2022.
APC values are presented with 95% confidence intervals (CI). Asterisk (*) indicates statistically significant APC values (p < 0.05).

Conclusion

Gastric carcinoma has poor prognosis, and although the general trend is decreasing across all socio-demographic areas, further research is required for targeted interventions and health policies for populations at high risk of dying.

References

1. Stahl KA, Olecki EJ, Dixon ME, et al. Gastric cancer treatments and survival trends in the United States. Current Oncology. 2020;28(1):138-151. doi:10.3390/curroncol28010017
2. Kumar RK, Raj SS, Shankar EM, Ganapathy E, Ebrahim AS, Farooq SM. Gastric carcinoma: a review on epidemiology, current surgical and chemotherapeutic options. Gastric Carcinoma-New Insights into Current Management. 2013/1/13 2013;12doi:10.5772/52138
3. Li C, Chen D, Yang H. Trends in incidence, survival and mortality of gastric cancer in the United States: a population-based study, 2001-2015. Asian Pacific Journal of Cancer Prevention: APJCP. 2023;24(6):2011-2020. doi:10.31557/APJCP.2023.24.6.2011
4. Hudler P, Komel R. Clinical Implications of Molecular Heterogeneity of Gastric Cancer. Gastric Cancer. 2017/9/20 2017;doi:10.5772/intechopen.69775
5. Ali H, Ishtiaq R, Tedder B, et al. Trends in mortality from gastrointestinal, hepatic, and pancreatic cancers in the United States: A comprehensive analysis (1999–2020). JGH Open. 2024;8(4):e13064. doi: 10.1002/jgh3.13064

Disclosure

No conflicts of interest to disclose.

Introduction

Dietary animal protein effect on gastric cancer (GC) taking Helicobacter pylori status into account has rarely been reported and has therefore been investigated in this study.

Aims & Methods

GC patients and healthy subjects were prospectively registered by 6 hospitals from October 2016 to December 2018. Multivariate analysis adjusted for many epidemiological factors (Model I) and additionally H. pylori (Model II) was conducted to investigate dietary protein effect on GC. Dietary animal protein groups included red meat, processed meat, white meat, eggs, and fishes.

Results

A total of 5,535 subjects (1,629 GCs) were enrolled. In Model I, red meat, fish, and eggs showed non-linear associations. Two serving/week for red meat, 1 serving/week for fish, 2-3 serving /week for egg was associated with the lowest risk of GC. Both low (aOR, 1.33) and high intake (aOR, 1.49) of red meat were associated with increased risk of GC. Both low (aOR, 1.76) and high intake (aOR, 1.74) of fish were associated with increased risk of GC. Both low (aOR, 3.07) and high intake (aOR, 1.33) of egg were associated with increased risk of GC. High intake of processed meat was associated with GC (adjusted odd ratio [aOR], 1.78; 95% CI, 1.27-2.49). Frequent intake of white meat was associated with GC risk (aOR, 1.67 for 1 serving/week, 2.15 for 2 servings/week, and 4.16 for ≥3 servings/week). In model II, these non-linear or positive association were sustained. Sub-analysis by sex showed similar association in both men and women.

Conclusion

Dietary animal proteins had non-linear or positive association with GC after adjusted for H. pylori. Nonlinear relationships of some food groups with GC suggests modest intake of such foods may reduce GC risk.

Disclosure

No COI

Introduction

Gastric cancer is the third leading cause of cancer-related death worldwide, and most cases of gastric cancer are diagnosed at an advanced stage with a poor prognosis. Early diagnosis of gastric cancer is important for increasing survival rates and improving treatment outcomes. However, there has been no accurate biomarker specific for gastric cancer. This study aims to elucidate the pathways involved in gastric cancer development by evaluating metabolic differences between intestinal metaplasia and gastric cancer and highlighting metabolic changes between the groups.

Aims & Methods

The tissues of intestinal metaplasia and gastric cancer were obtained from 37 gastric cancer patients. Multivariate metabolic analysis was performed using Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) to distinguish metabolic profiles and identify metabolomes that were significantly different between intestinal metaplasia and gastric cancer.

Results

PCA and PLS-DA significantly separated the gastric cancer tissue and intestinal metaplasia. Most of the metabolites related to steroid hormone biosynthesis were decreased, while metabolites that promote to cancer cell growth, such as s-Adenosyl-L-Methionine, S-adenosylmethioninamine, nopaline and N-acetylputrescine, were increased. In addition, the lysine degradation pathways demonstrated increases in L-lysine, L-lysopine and 5-Acetaminopentanoate, and N6-Acetyl-N6-hydroxy-L-lysine, which is consistent with the literature, but it requires further elucidation.

Conclusion

This is the first study to show metabolomic differences between the intestinal metaplasia and gastric cancer tissue using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The metabolites found in this study could be used as novel biomarkers for the early detection of gastric cancer with further validation research.

Introduction

The temporal trend of mortality rates among young individuals with gastric cancer has sparked a contentious debate over the past few decades. Additionally, there remains an ambiguous distribution alteration of disease burden among different countries.

Aims & Methods

​​​​This population-based systematic analysis was conducted to investigate changes in health inequality related to mortality caused by young gastric cancer from 1990 to 2019. We performed a secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 by extracting cross-sectional data on young gastric cancer (<40 years). The age-specific mortality rate was used to determine deaths attributed to young gastric cancer. A prediction of young gastric cancer mortality rate and case number up to 2030 was performed using the Norpred APC model. The slope index of inequality (SII) and the health concentration index were used to quantitatively measure absolute and relative changes in health inequalities, taking into account the socio-demographic indexes (SDI) level. The data was further analysed across different GBD regions and sexes.

Results

The global mortality rate of young gastric cancer declined from 1.61 (95% Uncertainty interval [UI]: 1.49 to 1.72) per 100,000 in 1990 to 0.94 (95% UI: 0.87 to 1.02) per 100,000 in 2019, with an annual rate of change -0.42% (95% Confidence interval (CI): -0.47 to -0.35). The projected data suggests that the number of global mortality case and rate of young gastric cancer would decrease to 24,450 and 0.761 per 100,000 by 2030. Countries belong to the lower 50% of SDI accounted for 49.9% and 52.3% of the global young gastric cancer deaths in 1990 and 2019, respectively. Although the absolute cross-national inequality (SII) of mortality rate fell from 0.133 (95%CI: -0.533 to 0.416) in 1990 to -0.239 (95%CI: -0.432 to -0.046) in 2019, the relative inequality (concentration index) for global young gastric cancer mortality increased from 1990 (−0.058, 95%CI: −0.532 to 0.416) to 2019 (−0.104, 95%CI: −0.526 to 0.317). The observed rise in absolute health inequality was evident in both sexes, but relative health inequality increased in females only. The regions of Sub-Saharan Africa (including Western and Southern), Central Asia, and Central Europe exhibited an increase in both absolute and relative health disparities in young gastric cancer mortality.

Conclusion

Although there has been a decline in the global young gastric cancer mortality rate, health inequality has increased over the past three decades, especially in females and some low SDI countries. It is imperative to prioritize efforts in addressing inequality to further reduce the global burden of young gastric cancer mortality.

Introduction

Gastric hyperplastic polyps (GHPs) carry a neoplastic transformation risk of up to 5%, with previous studies indicating an increased risk with larger polyp size. We aimed to evaluate the frequency and risk factors of its malignant transformation in a Portuguese cohort.

Aims & Methods

A multicenter retrospective cohort study was conducted including all patients undergoing endoscopic resection of GHPs ≥10mm from January 2013 to January 2024 in Portuguese tertiary reference centers. Patients with hereditary polyposis syndromes were excluded. Demographic, clinical, endoscopic, and histopathological data were collected.

Results

A total of 782 GHPs from eight centers were evaluated. The median age was 68 years (IQR 60-75), and 58.8% were female. Evidence of advanced gastritis stage (OLGIM≥3) and synchronous gastric neoplasia were present in 57 (10.2%) and 37 (4.7%) cases, respectively. The median lesion size was 15 mm (IQR 12-20), and most presented a polypoid morphology (96.8%). Most GHPs were removed by endoscopic mucosal resection (86.6%), followed by cold snare polypectomy (8.1%) endoscopic submucosal dissection (3.6%), and cold snare EMR (1.7%), achieving en-bloc resection in 677 cases (86.6%). Neoplastic transformation was observed in 33 polyps (4.2%) – 25 (3.2%) low/high-grade dysplasia and 8 (1.0%) adenocarcinoma; the resection was non-curative in 30.3% of cases.
In the multivariate analysis, OLGIM≥3 (OR 4.994, 95%CI 1.036-24.065), lesion size ≥25 mm (OR 7.973, 95%CI 7.973 (1.242-51.180), flat/depressed morphology (OR 9.57, 95%CI 1.096-83.712) and synchronous gastric neoplasia (OR 16.956, 95%CI 2.737-105.045) were independently associated with a higher risk of malignant transformation.

Conclusion

The risk of malignant transformation of GHPs in non-neglectable, with lesion size and morphology and concomitant precancerous gastric conditions/lesions being associated with a higher risk. Nevertheless, the rate of non-curative endoscopic resection is high. The identification of these features may help for optimizing and tailoring the selection of adequate endoscopic resection techniques and surveillance strategies in high-risk patients.

Introduction

Gastric squamous cell carcinoma (GSCC) is an aggressive rare histological subtype accounting for 0.04-0.5% only of all gastric tumors. Due to its scarcity, there are very few case reports in the literature and data are limited to institutional case series with significant variations. Thus, no recommendations for GSCC were published by the European Society of Medical Oncology or the National Comprehensive Cancer Network societies.

Aims & Methods

The aim of this study is to provide the literature with an updated evidence about this rare type for better understanding for its nature and establish a proper management strategy. Data were extracted from the Surveillance, Epidemiology and End Results (SEER) database for 784 patients diagnosed with primary GSCC with sequence 0 or 1 from 2000 to 2020. Patients were selected based on microscopic confirmation for the diagnosis . We used a rate session to calculate the age-adjusted trends as Percent Chance (PC) and Annual Percent Change (APC). We subdivided the patients according to the treatment modality into medical therapy, partial gastrectomy and total gastrectomy group, then followed by smaller subgroups (primary therapy and surgery with systemic therapy) . We used a survival session to calculate the relative survival. SPSS version 23 was used for data analysis, Kaplan-Meier and Log-Rank test for survival analysis. The results were considered significant when P <0.05.

Results

GSCC had 2000-2020 PC of -13.3 [APC= -0.5, 95% CI (-1.6: 0.6), P>0.05]. African-Americans had increased rate compared to Caucasians (RR=2.32, 95%CI: 1.96-2.73, P<0.0001). The overall 3-year and 5-year relative survival of GSCC were 21.7% and 17.4%. Out of 502 patients, 341(68.1%) received medical treatment only, 43(8.6%) had partial gastrectomy and 117(23.3%) had total gastrectomy with 5-year relative survival of 10.4%, 38.1% and 44.6% respectively; P<0.0001. Adjuvant chemoradiotherapy had similar 5-year survival compared to surgery with no systemic therapy while both had improved survival compared to surgical management with systemic chemotherapy only (43.4%, 51.5% and 22.9% respectively; P=0.07). Among the group who received systemic therapy only, primary chemoradiotherapy had improved 5-year relative survival compared to primary chemotherapy and primary radiotherapy (16.3%, 8.1% and 0.0%; P<0.0001).

Conclusion

GSCC is an aggressive malignancy with poor survival outcome. GSCC rates have decreased over the past 20 years. However, the rate in African-Americans is two folds greater to develop GSCC compared to Caucasians. Total gastrectomy had significant improved survival compared to partial gastrectomy and the medical treatment. These results highlights total gastrectomy as the modality of choice for primary GSCC. As adjuvant chemoradiotherapy had no significant benefit over surgery with no systemic therapy, we discourage the use of systemic therapy to avoid serious systemic side effects related to the systemic treatment for better quality of life after the surgical management.

References

1. de Lange G, Bouroumeau A, Coron E, Koessler T. Gastric squamous cell carcinoma: A rare malignancy, literature review and management recommendations (Review). Mol Clin Oncol. 2023;19(4):2–7.
2. Dong C, Jiang M, Tan Y, Kong Y, Yang Z, Zhong C, et al. The clinicopathological features and prognostic factors of gastric squamous cell carcinoma. Med (United States). 2016;95(34):1–7.
3. Akce M, Jiang R, Alese OB, Shaib WL, Wu C, Behera M, et al. Gastric squamous cell carcinoma and gastric adenosquamous carcinoma, clinical features and outcomes of rare clinical entities: A National Cancer Database (NCDB) analysis. J Gastrointest Oncol. 2019;10(1):85–94.