Search Results (41)

Background: Epstein–Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subgroup with potential responsiveness to immunotherapy approved for programmed death-ligand 1 (PD-L1)-positive gastric cancer. This retrospective study aimed to assess the prevalence and association between EBVaGC and PD-L1 positivity among patients with gastric adenocarcinoma treated at a university hospital in Southern Thailand from January 2017 to October 2023. Methods: The EBV status of the patients and PD-L1 expression were determined using in situ hybridization and immunohistochemistry, respectively. Results: The prevalence of EBVaGC was 4.5% among 132 patients, whereas 9.1% of patients exhibited a PD-L1 combined positive score (CPS) of ≥1, with no significant association observed between them. EBVaGC was more prevalent in males, non-antral tumors, diffuse/mixed histologic subtypes, and poorly differentiated tumors. Median overall survival for patients with EBVaGC and PD-L1 CPS ≥ 1 was 9.48 and 14.19 months, respectively, compared with 10.32 and 9.79 months for those with non-EBVaGC (hazard ratio: 1.24; 95% CI: 0.50–3.04; p = 0.645) and PD-L1 CPS < 1 (hazard ratio: 0.82; 95% CI: 0.40–1.69; p = 0.590), respectively. Conclusions: Our findings revealed a low prevalence of EBVaGC and PD-L1 positivity in Thailand, with no significant association or survival impact observed. These findings highlight the regional variation in these biomarkers and support EBV as an independent biomarker from PD-L1. However, further research, particularly studies evaluating immunotherapy outcomes, is warranted to clarify the predictive and clinical significance of EBV in gastric cancer. Full article

Background: Helicobacter pylori is a Gram-negative bacterium responsible for various gastrointestinal diseases, including peptic ulcers and gastric cancer. Despite available antibiotic therapies, increasing resistance to clarithromycin—a key antibiotic in eradication regimens—poses a significant challenge. This resistance is primarily linked to point mutations in the 23S rRNA gene, particularly A2143G, A2142G, and A2142C, which hinder clarithromycin binding, reducing its bacteriostatic efficacy. This study aimed to assess the prevalence and variability of clarithromycin resistance mutations in pediatric patients from Bydgoszcz, Poland. Methods: A total of 45 gastric biopsy samples from pediatric patients were analyzed using the Bosphore^® Helicobacter pylori Genotyping Kit v1 to detect clarithromycin resistance-associated mutations. Results: Among the 45 tested samples, 30 were classified as wild-type, while 12 contained resistance-associated mutations. The most frequently detected mutation was A2143G (58.3%), followed by A2142G (33.3%). One sample exhibited both A2142G and A2143G mutations, and another contained a mixture of wild-type and mutant strains. The A2142C mutation was not detected in any sample. Conclusions: Our findings confirm the predominance of A2143G among clarithromycin-resistant H. pylori strains, consistent with global trends. The detection of both mutant and wild-type strains in a single patient highlights potential co-infections or subpopulations with varying resistance profiles. Continuous surveillance and improved diagnostic tools are crucial for optimizing treatment strategies. Tailored eradication protocols based on resistance profiling are necessary to enhance treatment efficacy and mitigate the spread of resistant strains. Further research is needed to understand the clinical implications of mixed infections and double mutations in H. pylori resistance development. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated. Hence, our aim was to investigate the prevalence of histological subtypes and their possible association with HGD/C concerning morphologically different IPMNs. Methods: This was a retrospective review of demographics, risk factors, and histological features in a surgical cohort of patients having undergone resection for suspect malignant IPMNs at a high-volume tertiary center from 2007 to 2017. Results: A total of 273 patients were resected for IPMNs from during the study period, of which 188 were included in the final analysis. With sex- and age-adjusted multivariable logistic regression analysis across the entire cohort, gastric foveolar subtypes were associated with a reduced prevalence of HGD/C (OR = 0.30; 0.11–0.81, 95% CI, 95%CI; p = 0.01). With univariable logistic regression analysis, in the BD-IPMN subgroup, the pancreaticobiliary subtype was associated with an increased prevalence of HGD/C (OR = 18.50, 1.03–329.65, 95% CI; p = 0.04). In MD- and MT-IPMNs, the gastric foveolar subtype was associated with a decreased prevalence of HGD/cancer (OR = 0.30, 0.13–0.69, 95% CI; p = 0.004). Conclusions: In MD and MT-IPMNs, the gastric-foveolar subtype is associated with a lower prevalence of HGD/C, possibly identifying in such a high-risk group, a subgroup with more indolent behavior. In BD-IPMNs, the pancreaticobiliary subtype is associated with a higher prevalence of HGD/C, conversely identifying among those patients, a subgroup deserving special attention. Full article

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. Full article

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin’s functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin’s function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation. Full article

Due to its high aggressiveness and polyclonal tumor state, stomach cancer is considered a severe health problem. In this study, we analyzed Her2 and Ki67 in correlation with patient data for the possibility of prognostic factors. The study included 48 cases of gastric tumors that had been surgically treated in a period of five years. The percentage was statistically significant for intestinal-type adenocarcinomas located in the medio-gastric region (p = 0.05); in the diffuse subtype, there were no Her2 positive samples, and in the mixed subtype only one out of three samples was Her2 positive. Our results confirm the existing data, and we can conclude that this link can be considered a prognostic factor in the progression and treatment effectiveness. Full article

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) and EGFR-activating mutations. Proton-pump inhibitors decreased dacomitinib exposure. This analysis summarizes the effect of Histamine-2 receptor antagonists (H2RAs) on dacomitinib exposure. A within-patient comparison of the steady-state trough concentrations (C_trough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RAs was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption physiologically based pharmacokinetic (PBPK) model was constructed and verified using clinical pharmacokinetic (PK) data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib’s PKs. The adjusted geometric mean of the dacomitinib C_trough,ss of the dacomitinib parent, metabolite and active moiety following co-administration with an H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without an H2RA (p > 0.05). The PBPK modeling showed negligible change in dacomitinib maximum concentration (C_max) and area under the drug concentration–time curve (AUC) over 0–24 h after H2RA administration when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure. Full article

Klotho proteins, αKlotho, βKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and βKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools. Full article

Background: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. Methods: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. Results: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. Conclusions: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications. Full article

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear. Full article

This study aims to identify the background factors and experiences of patients with cancer with eating-related problems who require nutrition counselling. Using a mixed-methods approach, this secondary analysis study was conducted on patients with head and neck, oesophageal, gastric, colorectal, or lung cancers who were receiving outpatient chemotherapy. They completed a questionnaire measuring nutrition impact symptoms, eating-related distress, and quality of life (QOL). Patients who required nutrition counselling were interviewed to identify the specific issues they experienced. We reported on nutritional status and nutrition impact symptoms in a previous study. Of the 151 participants, 42 required nutrition counselling. Background factors associated with nutrition counselling were related to the following psychosocial variables: small number of people in the household, undergoing treatment while working, low QOL, and eating-related distress. Four themes were extracted from the specific issues experienced by patients: motivation for self-management, distress from symptoms, seeking understanding and sympathy, and anxiety and confusion. The desire for nutrition counselling was attributable to ‘anxiety caused by the symptoms’ and ‘confusion about the information on eating’. Healthcare professionals should promote multidisciplinary collaboration after considering the factors associated with the required nutrition counselling to provide nutritional support. Full article

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [¹⁸F]FDG-PET radiomics. Methods: [¹⁸F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [¹⁸F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis. Full article

(1) Background: A major challenge for post-discharged gastric cancer patients following gastrectomy is the impact of the anatomy change on decreased oral intake, nutritional status, and, ultimately, quality of life. The purpose of this study is to examine the feasibility and preliminary effects of an individualized mHealth nutrition (iNutrition) intervention in post-discharged gastric cancer patients following gastrectomy. (2) Methods: A mixed-method feasibility study with a parallel randomized controlled design was conducted. Patients were randomly assigned to either the iNutrition intervention group (n = 12) or the control group (n = 12). Participants completed measures at baseline (T0), four (T1), and twelve weeks (T2) post-randomization. (3) Results: Recruitment (33%) and retention (87.5%) rates along with high adherence and acceptability supported the feasibility of the iNutrition intervention for post-discharged gastric cancer patients following gastrectomy, echoed by the qualitative findings. The iNutrition intervention significantly improved participants’ nutritional behavior (p = 0.005), energy intake (p = 0.038), compliance with energy requirements (p = 0.006), and compliance with protein requirements (p = 0.008). (4) Conclusions: The iNutrition intervention is feasible and potentially benefits post-discharged gastric cancer patients following gastrectomy. A larger trial is required to establish the efficacy of this approach. Trial Registration: 19 October 2022 Chinese Clinical Trial Registry, ChiCTR2200064807. Full article

Gastric cancer (GC) is the fifth most common type of cancer and the fourth leading cause of cancer death. In Brazil, GC has a high incidence and mortality rates, and it is highly variable by region. The Amazon region has significant rising rates among all Brazil regions. Only very few studies have evaluated the association between genetic variants and the risk of gastric cancer in the Brazilian Amazon population. Therefore, this study aimed to investigate associations between single nucleotide polymorphisms of miRNA processing genes and the risk for GC in this population. Potentially functional single nucleotide polymorphisms from miRNA processing genes were genotyped in 159 cases and 193 healthy controls by QuantStudio Real Time PCR. According to our findings, the genotype GG of the variant rs10739971 presents a lower risk to the development of GC in comparison to the remaining genotypes (p = 0.000016; OR = 0.055; 95% CI = 0.015–0.206). This is the first study to report the association of pri-let-7a-1 rs10739971 with GC in the Brazilian Amazon population, which is a highly mixed population with a unique genetic constitution that is different from other populations that are studied in the vast majority of scientific research. Full article

Signet ring cell adenocarcinomas (SRCCs) are a rare histological adenocarcinoma subtype, classically thought to have a worse prognosis than conventional adenocarcinomas. The majority of these cancers occur in the stomach, colon, and rectum. Their rarity means that most epidemiological studies into their pathology are often underpowered, and interpretations from these reports are mixed. In this study, we use the Surveillance, Epidemiology, and End Results Program (SEER) database to examine the effects of tumor localization, age, and stage on gastric and colorectal cancer outcomes. For early onset localized and regional gastric cancers, SRCCs have the same overall risk of mortality compared to conventional adenocarcinomas. Over the age of 50 years, SRCCs have worse outcomes across all stages. Gastric SRCCs are 2–3-fold more likely in younger patients, and more heavily favor the distal stomach. Like conventional adenocarcinomas, proximal gastric SRCCs have decreased survival. Across all ages, stages, and locations, colorectal SRCCs have worse outcomes. SRCCs favor the right colon, but outcomes are significantly worse for the left colon and rectal cancers. Relative to adenocarcinomas, colorectal SRCCs have the worst outcomes in younger patients. Overall, these results provide insights into SRCC disease patterns that cannot be surmised outside of population-level data. Full article