Patients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent ...(metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear.
In this prospective, double-blind, placebo-controlled, randomized trial, we assigned 470 patients who had undergone endoscopic resection of early gastric cancer or high-grade adenoma to receive either H. pylori eradication therapy with antibiotics or placebo. Two primary outcomes were the incidence of metachronous gastric cancer detected on endoscopy performed at the 1-year follow-up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3-year follow-up.
A total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). During a median follow-up of 5.9 years, metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03). Among the 327 patients in the subgroup that underwent histologic analysis, improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). There were no serious adverse events; mild adverse events were more common in the treatment group (42.0% vs. 10.2%, P<0.001).
Patients with early gastric cancer who received H. pylori treatment had lower rates of metachronous gastric cancer and more improvement from baseline in the grade of gastric corpus atrophy than patients who received placebo. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT02407119 .).
Background
Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the ...association between the cumulative exposure to IFG and gastrointestinal cancer risk.
Methods
The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0–4) was based on the number of IFG diagnoses over 4 years.
Results
The median follow‐up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio aHR, 1.05; 95% confidence interval CI, 1.01–1.08; score 2: aHR, 1.08; 95% CI, 1.04–1.12; score 3: aHR, 1.09; 95% CI, 1.05–1.14; score 4: aHR, 1.12; 95% CI, 1.06–1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus).
Conclusions
Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose‐dependent manner.
Plain Language Summary
Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers.
However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear.
A frequent diagnosis of impaired fasting glucose was dose‐dependently associated with a higher risk of developing overall gastrointestinal cancer.
Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose.
Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden.
Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.
Cumulative exposure to impaired fasting glucose is dose‐dependently associated with an increased risk of gastrointestinal cancer, and persistent exposure also increases risks of individual cancer types.
Background
Although depression is associated with poor treatment outcomes in patients with cancer, little is known about whether lifestyle modifications could help prevent depression. The authors ...aimed to identify the effect of lifestyle modifications, including smoking cessation, alcohol abstinence, and starting regular physical activity, on new‐onset depression in patients with gastric cancer who underwent surgery.
Methods
By using the Korean National Health Insurance Service database, patients with gastric cancer who underwent surgery between 2010 and 2017 were identified. Self‐reported lifestyle behaviors within 2 years before and after surgery were analyzed using the health examination database. Patients were classified according to changes in lifestyle behaviors, and their risk of new‐onset depression was compared.
Results
Among 18,902 patients, 2302 (12.19%) developed depression (26.00 per 1000 person‐years). Smoking cessation (hazard ratio HR, 0.77; 95% confidence interval CI, 0.66–0.91) and alcohol abstinence (HR, 0.79; 95% CI, 0.69–0.90) were associated with reduced risk of depression development compared with persistent smoking and persistent drinking, respectively. Starting regular physical activity was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (1 point each for not smoking, not drinking, and being physically active), the risk of depression tended to decrease as lifestyle scores increased from 0 points (reference) to 1 point (HR, 0.69; 95% CI, 0.55–0.83), 2 points (HR, 0.60; 95% CI, 0.50–0.76), and 3 points (HR, 0.55; 95% CI, 0.45–0.68).
Conclusions
Smoking cessation and alcohol abstinence are associated with reduced risk of developing depression in patients with gastric cancer who undergo surgery.
Smoking cessation and alcohol abstinence are associated with reduced risk of developing depression in patients with gastric cancer who undergo gastrectomy compared with persistent smoking and persistent drinking, respectively. Health care providers should encourage patients to quit smoking and abstain from alcohol considering the potential effects of lifestyle modification on preventing depression.
Background
Metachronous gastric cancer (MGC) may develop in patients undergoing curative endoscopic submucosal dissection for early gastric cancer. As gastritis and intestinal metaplasia are notable ...precursors to gastric cancer, we assessed MGC risk using the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM) systems.
Methods
This retrospective cohort study classified the OLGA and OLGIM stages for 916 patients who had undergone endoscopic submucosal dissection for early gastric cancer between 2005 and 2015. MGC development was followed up until 2020 and risk factors were evaluated using the Cox proportional hazards regression analysis.
Results
During a median follow-up of 94 months, MGC developed in 120 subjects. OLGA stages II ~ IV were significantly associated with increased MGC risk (hazard ratio HR 1.83, 95% confidence interval CI 1.05–3.19; HR 2.31, 95% CI 1.22–4.38; HR 2.36, 95% CI 1.16–4.78) in multivariable analysis, even after adjusting for the well-known positive predictor of
Helicobacter pylori
eradication. OLGIM stages II ~ IV also showed significant association (HR 2.86, 95% CI 1.29–6.54; HR 2.94, 95% CI 1.34–6.95; HR 3.64, 95% CI 1.60–8.29). 5-year cumulative incidence increased with each stage.
Helicobacter pylori
-eradicated patients with OLGIM stages 0 ~ II had significantly less MGC than non-eradicated patients (4.5% vs 11.8%,
p
= 0.022), which was not observed with OLGIM stages III ~ IV.
Conclusions
High OLGA and OLGIM stages are independent risk factors for metachronous gastric cancer, with the OLGIM staging system being a better predictor. Patients with OLGIM stages 0 ~ II are a subgroup that may benefit more from
Helicobacter pylori
eradication.
Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma, but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 ...activity and inhibition were examined in gastric adenocarcinoma cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44
gastric adenocarcinoma CSCs compared with unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78%-81%, and prevented tumor initiation in immunodeficient mice. Gastric adenocarcinoma CSCs had increased expression of the EMT transcription factor Slug, 4.4- to 8.3-fold greater migration, and 4.2- to 12.6-fold greater invasion than unselected cells, and these increases could be blocked completely with Rac1 inhibition. Gastric adenocarcinoma spheroid cells were resistant to 5-fluorouracil and cisplatin chemotherapy, and this chemotherapy resistance could be reversed with Rac1 shRNA or NSC23766. The PI3K/Akt pathway may be upstream of Rac1, and JNK may be downstream of Rac1. In the MKN-45 xenograft model, cisplatin inhibited tumor growth by 50%, Rac1 inhibition by 35%, and the combination by 77%. Higher Rac1 activity, in clinical specimens from gastric adenocarcinoma patients who underwent potentially curative surgery, correlated with significantly worse survival (
= 0.017). In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy.
In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance.
.
Background
While cancer patients are at an increased risk of cardiovascular disease (CVD), the role of modifiable risk factors remains poorly understood. This study investigated whether lifestyle ...modifications affect CVD development in gastric cancer patients who undergo surgery.
Methods
Using data from the Korean National Health Insurance Service (NHIS), gastric cancer patients who underwent surgery from 2010 to 2017 were identified. Lifestyle behaviours, surveyed within 2 years before and after surgery were analysed. Incident CVD, defined as a composite of myocardial infarction and stroke, was compared among subgroups of lifestyle behaviour changes.
Results
Among 22,211 gastrectomy patients, 628 (2.8%) developed CVD (5.68/1000 person‐years). Persistent smokers (HR: 1.72, 95% CI: 1.33–2.22) and new smokers (HR: 1.85, 95% CI: 1.04–3.30) faced higher CVD risks than non‐smokers, with an especially pronounced risk in persistent‐smoking females (HR: 3.89, 95% CI: 1.20–12.62). Smoking cessation showed no significant risk difference compared to non‐smokers (HR: 1.16, 95% CI: 0.93–1.43). Female new drinkers had a higher CVD risk than non‐drinking females (HR: 2.89, 95% CI: 1.06–7.88), while men did not show such association. Changes in physical activity, when compared to physical inactivity, were not associated with CVD risk.
Conclusion
Gastric cancer patients who smoked after surgery were more likely to develop CVD irrespective of their prior smoking status, with a notable vulnerability in persistent female smokers. Smoking cessation could potentially mitigate CVD risk to levels observed in non‐smokers. Alcohol intake should be avoided following surgery, especially for female gastric cancer patients.
Gastric cancer patients who smoke after surgery are more likely to develop cardiovascular disease (CVD) irrespective of their prior smoking status, while smoking cessation could potentially mitigate CVD risk to levels observed in non‐smokers. Female gastric cancer patients, who started consuming alcohol after gastrectomy, have higher CVD risk compared to non‐drinking females.
Edible insects have received global attention as an alternative protein-rich food. However, their structural characteristics make them difficult to digest. To overcome this obstacle, we assessed the ...techno-functional properties of three protein concentrates from the cricket
. Freeze-dried
powder was defatted using ethanol, hexene, or acetone as solvents, and the techno-functional properties (protein solubility, water and oil holding capacity, foaming properties, emulsion capacity, and gel formation) of the protein concentrates were determined. Freeze-dried
powder comprised approximately 17.3% crude fat and 51.3% crude protein based on dry weight. Ethanol was the most effective solvent for reducing the fat content (from 17.30% to 0.73%) and increasing the protein content (from 51.3% to 62.5%) of the concentrate. Techno-functionality properties drastically differed according to the defatting solvent used and foaming properties were most affected. Thus, the techno-functional and whole properties must be considered for proper application of edible insects to achieve global food sustainability.
Disulfiram (DSF), which is used to treat alcohol dependence, has been reported to have anti-cancer effects in various malignant tumors. In this study, we investigated the anti-cancer effects and ...mechanism of DSF in HNSCC.
Head and neck squamous carcinoma cell lines (FaDu and Hep2) were used to analyze the anti-cancer effects of DSF. The anti-cancer effects of DSF were confirmed in vivo using a xenograft tumor model.
The anti-cancer effects of DSF in HNSCC were found to be copper (Cu) dependent. Specifically, DSF/Cu markedly inhibited HNSCC at a concentration of 1 μM. After DSF/Cu administration, production of reactive oxygen species (ROS) was remarkable starting at 0.5 μM, suggesting that the inhibitory effects of DSF/Cu on HNSCC are mediated through the formation of ROS. The levels of phospho-JNK, phospho-cJun and phospho-p38 were increased after DSF/Cu treatment while levels of phospho-Akt were decreased. These results suggested that the inhibitory effects of DSF/Cu on HNSCC cells involve ROS formation and down-regulation of Akt-signaling. Through these molecular mechanisms, DSF ultimately induce the inhibitory effects on HNSCC cell lines mainly through autophagic cell death, not apoptotic cell death. Lastly, we investigated the clinical relevance of DSF/Cu using a HNSCC xenograft animal model, which showed that tumor growth was remarkably decreased by DSF (50 mg/kg injection).
In treating patients with HNSCC, DSF may contribute to improved HNSCC patient's survival. The characteristic anti-cancer effects of DSF on HNSCC may suggest new therapeutic potential for this medication in HNSCC patients.
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