Search Results (76)

Autoimmune gastritis (AIG) is an uncommon and often underestimated condition in children, characterized by chronic stomach inflammation leading to the destruction of oxyntic glands with subsequent atrophic and metaplastic changes. This condition is associated with hypo-/achlorhydria, impairing iron and vitamin B12 absorption. The pathogenesis involves the activation of helper type 1 CD4+/CD25-T-cells against parietal cells. Clinical manifestations in children are not specific and include abdominal pain, bloating, nausea, vomiting, and iron deficiency anemia (IDA). The disease is also linked to an increased risk of pernicious anemia, intestinal-type gastric cancer, and type I neuroendocrine tumors. AIG is often diagnosed through the presence of autoantibodies in the serum, such as parietal cell (APCA) and intrinsic factor (IF) antibodies. However, therapeutic recommendations for pediatric AIG are currently lacking. We aim to present two clinical cases of pediatric-onset AIG, highlighting the heterogeneous clinical manifestations and the challenges in diagnosis with the support of an updated literature review. A 9-year-old girl presented with refractory IDA, initial hypogammaglobulinemia, and a 12-year-old boy was initially diagnosed with eosinophilic esophagitis. Both cases underline the importance of considering AIG in children with chronic gastrointestinal symptoms and gastric atrophy. Diagnostic workup, including endoscopy and serological tests, is crucial for accurate identification. A better understanding of this condition is imperative for timely intervention and regular monitoring, given the potential long-term complications, including the risk of malignancy. These cases contribute to expanding the clinical spectrum of pediatric AIG and highlight the necessity for comprehensive evaluation and management in affected children. Full article

Objectives: The objective of this study was to assess the relationship of VEGF-C and LVD with pathoclinical factors of potential prognostic value and with the survival time of gastric cancer patients. Materials and methods: A total of 103 radically operated patients for gastric cancer who did not undergo neoadjuvant therapy were included in this study. The minimum follow-up period after surgery was 61 months. VEGF-C and lymphatic vessels were immunohistochemically determined using antibodies, including VEGF-C (c-20) sc 1881-Goat Polyclonal IgG (Santa Cruz Biotechnology) and Podoplanin D2-40 Mouse Monoclonal Antibody (ROCHE). The relationship between VEGF-C expression in gastric adenocarcinoma cells and the density of lymphatic vessels at the periphery of the primary tumor was assessed, along with the relationships of VEGF-C and LVD with selected pathoclinical parameters of gastric cancer and prognosis. Results: VEGF-C overexpression was associated with increased LVD (Mann–Whitney U test, p = 0.03) and the Lauren intestinal type of cancer (Pearson’s chi-square test, p < 0.001). Increased LVD was more often associated with cancers located beyond the cardia (Mann–Whitney U test, p = 0.04). We did not demonstrate an association of VEGF-C or LVD with OS or with prognostic features, such as pT, pN, or pTNM staging. However, in the Lauren intestinal type of cancer, VEGF-C overexpression correlated with shorter OS (log-rank, p = 0.01) and, at the level of p = 0.05 in multivariate analysis, it had an independent negative prognostic value. Conclusions: Peritumoral overexpression of VEGF-C in primary gastric cancer tumors is associated with increased LVD. The Lauren intestinal type of cancer is associated with VEGF-C overexpression. The overexpression of VEGF-C in intestinal-type gastric cancer is associated with worse prognosis. Full article

Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host’s dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions. Full article

Background/Objectives: Gastric cancer remains a leading cause of cancer mortality worldwide. Reliable biomarkers are crucial for early detection, prognostication, and therapy monitoring. While classical tumor markers such as carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA72-4, and alpha-fetoprotein (AFP) are used in clinical practice, their accuracy can be limited. Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in tumor progression, yet its relationship with established gastric cancer tumor markers has not been fully clarified. This study aimed to determine whether elevated TNF-α correlates with key tumor markers and disease stage in gastric cancer. Methods: In this prospective observational study, we enrolled 80 gastric cancer patients and 20 non-neoplastic controls. Baseline clinical data, laboratory parameters, and tumor markers (CEA, CA19-9, CA72-4, AFP) were recorded. TNF-α concentrations were measured using enzyme-linked immunosorbent assays. Correlation analyses and multivariate regression were performed to assess the relationship of TNF-α with tumor markers, inflammatory indices, and disease stage. Results: TNF-α was significantly elevated in gastric cancer patients (median 4.5 pg/mL) compared to controls (2.9 pg/mL). TNF-α showed a robust correlation with CA19-9 (rho = 0.502) and CA72-4 (rho = 0.385), and a moderate correlation with CEA (rho = 0.279). TNF-α concentrations were highest in Stage IV disease and in the intestinal-type histology. In regression analysis, only CA19-9 and CA72-4 remained independent predictors of TNF-α after controlling for clinical confounders. Conclusions: TNF-α is strongly associated with CA19-9 and CA72-4 and rises with advancing stage, highlighting its potential as an adjunct marker for assessing gastric cancer burden. These findings provide a rationale for further research on TNF-α as both a prognostic biomarker and a possible therapeutic target in gastric cancer. Full article

Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes. Methods: A total of 61 GI NET cases were identified from our institution from 2019–2024. In total, twenty-seven review papers, ten population-based/multicenter/outcome studies, six case reports, and one case series were reviewed for the literature review. Results: The incidence of GI NETs at our institution was higher than the known epidemiology of GI NETs. Small intestine NETs were one of the most common sites of GEP-NETs at our institution, with only one of nineteen cases being grade 3 poorly differentiated neuroendocrine carcinoma. All cases of colonic and rectal NETs had good clinical outcomes consistent with findings from the literature. Most of the gastric NETs were type 1 and had benign courses of disease, except for one case with an intermediate grade and metastatic liver lesions. One case of esophageal neuroendocrine carcinoma (E-NEC) showed a complete response to chemotherapy despite a significant tumor burden on presentation and high-grade pathology, while another case of ENEC had recurrent disease despite systemic therapy. Conclusions: While the role of surgery or endoscopic resection is limited to localized tumors, combined treatment with chemoradiation can significantly improve patient outcomes, especially in high-grade, poorly differentiated tumors. Further studies are needed to establish systemic (i.e., chemotherapy and radiation) treatment strategies for poorly differentiated GI NETs. Full article

Gastrointestinal (GI) cancers, which mainly include malignancies of the esophagus, stomach, intestine, pancreas, liver, gallbladder, and bile duct, pose a significant global health burden. Unfortunately, the prognosis for most GI cancers remains poor, particularly in advanced stages. Current treatment options, including targeted and immunotherapies, are less effective compared to those for other cancer types, highlighting an urgent need for novel molecular targets. NEK (NIMA related kinase) kinases are a group of serine/threonine kinases (NEK1-NEK11) that play a role in regulating cell cycle, mitosis, and various physiological processes. Recent studies suggest that several NEK members are overexpressed in human cancers, including gastrointestinal (GI) cancers, which can contribute to tumor progression and drug resistance. Among these, NEK2 stands out for its consistent overexpression in all types of GI cancer. Targeting NEK2 with specific inhibitors has shown promising results in preclinical studies, particularly for gastric and pancreatic cancers. The development and clinical evaluation of NEK2 inhibitors in human cancers have emerged as a promising therapeutic strategy. Specifically, an NEK2 inhibitor, T-1101 tosylate, is currently undergoing clinical trials. This review will focus on the gene expression and functional roles of NEKs in GI cancers, as well as the progress in developing NEK inhibitors. Full article

Background: Gastric cancer is one of the most prevalent gastrointestinal cancers. Mortality is high, and improved treatments are needed. A better understanding of the pathophysiology of the disease and discovery of biomarkers for targeted therapies are paramount for therapeutic progress. CDX2, a transcription factor of hindgut specification, is induced in several gastric cancers, especially with intestinal differentiation, and could be helpful for defining sub-types with particular characteristics. Methods: Gastric cancers with induced CDX2 mRNA expression were identified from the gastric cohort of The Cancer Genome Atlas (TCGA) and were compared with cancers that had no CDX2 mRNA induction. Induced CDX2 mRNA expression was defined as mRNA expression z-score relative to all samples above 0, and non-induced CDX2 mRNA expression was defined as mRNA expression z-score relative to all samples below −1. Results: Patients with gastric cancers with CDX2 mRNA induction were older, had less frequently diffuse histology, and more often had mutations in TP53 and KMT2B and amplifications in MYC. CDX2 induction was correlated with HNF4α induction and was reversely correlated with SOX2. Gastric cancers with CDX2 mRNA induction showed lower PD-L1 expression than cancers with lower CDX2 expression but did not differ in CLDN18 mRNA expression. Progression-free and overall survival of the two groups was also not significantly different. Conclusion: Gastric cancers with CDX2 mRNA induction displayed specific characteristics that differentiate them from cancers with no CDX2 induction and could be of interest for optimizing current and future therapies. Full article

Background/Objectives: Since 2013, eradication therapy for Helicobacter pylori gastritis (Hp-ET) has been covered by the National Health Insurance of Japan. Recently, the risk of post-eradication gastric cancer (pE-GC) has increased. pE-GC includes cancers that develop immediately and several years after Hp-ET. Therefore, we aimed to clarify the endoscopic and histological characteristics of late types of pE-GCs. Method: One hundred patients with differentiated cancers detected after Hp-ET who underwent endoscopic submucosal dissection from 2015 to 2023 were compared. Patients were divided into two groups; the immediate group (n = 69), with cancer detected within 6 years, and the delayed group (n = 31), with cancer detected within >6 years after Hp-ET. The background mucosa and tumor mucosa were examined individually. The endoscopic findings were as follows: enlarged folds, map-like redness, intermediate zone irregularity, and the presence of a regular arrangement of collecting venules and a light blue crest (background); an irregular surface structure, an irregular vascular pattern, an irregular surface pattern, and a gastritis-like appearance (tumor). The histological findings were as follows: a low remnant rate of the fundic glands, intestinal metaplasia (IM), crypt enlargement, and neutrophil infiltration (background); mosaicism, the elongation of noncancer ducts, and an overlying non-neoplastic epithelium (tumor). Results: There was no significant difference regarding the background mucosa and tumor mucosa between the two groups. In the delayed group, the remnant rate of the fundic glands was 19.8 ± 15.6%, and IM was 87.1% (27/31). Further, 90.3% (28/31) of the patients exhibited persistent neutrophil infiltration. Conclusion: This study suggested that patients with a low remnant rate of the fundic gland and IM and persistent mucosal inflammation were at high risk for developing pE-GCs. 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

Causal networks are important for understanding disease signaling alterations. To reveal the network pathways affected in the epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to the poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) were analyzed. The network pathways in GC were analyzed using Ingenuity Pathway Analysis (IPA). The analysis of the probe sets in which the gene expression had significant differences between diffuse- and intestinal-type GC in RNA sequencing of the publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of EMT regulation via the growth factors pathway, the coronavirus pathogenesis pathway, and vorinostat. The network had RNA–RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-223, mir-25, mir-27, mir-29, and mir-34. The molecular networks revealed in the study may lead to identifying drug targets for GC. 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

(1) Background: We aimed to identify the possible relationship between various diseases of the upper digestive system and colon polyps by analyzing patients with gastric polyps and evaluating the cancers and diseases accompanying the polyps. (2) Methods: Each patient’s age; gender; polyp type and size; presence of Helicobacter pylori (H. pylori), atrophic gastritis, and intestinal metaplasia; status of whether cancer developed during follow-up; status of whether a colonoscopy was performed or not; and colon pathologies detected during colonoscopy were analyzed retrospectively using hospital records. (3) Results: Between the study dates, 19,214 esophagogastroduodenoscopies were performed in the endoscopy unit of our hospital. Gastric polyps were detected in 178 (0.9%) patients. No significant relationship was found between the gastric polyp size and the occurrence of gastric cancer or gastrointestinal system malignancy (p > 0.05). A colonoscopy was performed in 86 of the 178 patients who underwent gastroscopy. The frequency of polyp detection during colonoscopy was statistically significantly higher in patients with gastric polyps than in patients without gastric polyps (p < 0.001). (4) Conclusions: New prospective studies are needed regarding the relationship between gastric polyps and gastrointestinal system diseases. Going forward, a colonoscopy will be required in gastric polyp patients, especially with FGP. Full article

Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation. Full article

Early gastric cancers (EGCs) are confined to the gastric mucosa and submucosa irrespective of lymph node metastases and constitute only a minor proportion of gastric cancer in Western countries. We aimed to characterize EGCs and assess the survival of EGC in Central Norway during 2001–2016. A retrospective population-based study on 1205 patients with gastric cancer was performed. At the time, surgical resection was the standard treatment, and 88 (7.3%) EGCs were identified. Histopathological specimens were re-examined, and the eCura score and survival were evaluated. The number of gastric cancers declined (p = 0.010), but the relative proportion of EGC was unchanged during the study period. EGCs were more often of the Lauren intestinal type (p < 0.001) compared with controls. A significant proportion (9.4%, n = 5) of the patients with a low-risk eCura had lymph node metastases, whereas further exclusion of tumors with histological ulceration or SM2 invasion identified an N0 cohort. The median survival for EGC patients was 117.1 months (95% CI 99.8–134.3) and the 5-year overall survival was 75%. Twelve deaths were cancer-related, either due to postoperative complications (5.7%, n = 5) or cancer recurrence (8%, n = 7). In conclusion, EGCs constituted a minor but constant proportion of gastric cancers. eCura alone was insufficient in predicting patients with pN0 disease. Full article

There are a limited number of clinically useful serum biomarkers to predict tumor onset or treatment response in gastric cancer (GC). For this reason, we explored the serum proteome of the gp130^Y757F murine model of intestinal-type gastric cancer (IGC). We identified 30 proteins with significantly elevated expression in early gp130^Y757F IGC and 12 proteins that were significantly elevated in late gp130^Y757F IGC compared to age- and gender-matched wild-type mice. Within these signatures, there was an overlap of 10 proteins commonly elevated in both early- and late-stage disease. These results highlight the potential to identify serum biomarkers of disease stage. Since IGC in the gp130^Y757F model can be reversed following therapeutic inhibition of Interleukin (IL)-11, we explored whether the protein signatures we identified could be used to monitor tumor regression. We compared two different therapeutic modalities and found 5 proteins to be uniquely differentially expressed between control animals and animals halfway through treatment, with 10 differentially expressed at the end of treatment. Our findings highlight the potential to identify reliable biomarkers to track IGC tumor regression in response to treatment. Full article