Search Results (54)

Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article

Background/Objectives: Patients with stage IV gastric cancer who develop chronic intestinal failure require home parenteral nutrition (HPN). This study aimed to evaluate the prognostic relevance of nutritional and immune–inflammatory biomarkers and to construct an individualised survival prediction model using machine learning techniques. Methods: A secondary analysis was performed on a cohort of 410 patients with TNM stage IV gastric adenocarcinoma who initiated HPN between 2015 and 2023. Nutritional and inflammatory indices, including the Controlling Nutritional Status (CONUT) score and lymphocyte-to-monocyte ratio (LMR), were assessed. Independent prognostic factors were identified using Cox proportional hazards models. A Random Survival Forest (RSF) model was constructed to estimate survival probabilities and quantify variable importance. Results: Both the CONUT score and LMR were independently associated with overall survival. In multivariate analysis, higher CONUT scores were linked to increased mortality risk (HR = 1.656, 95% CI: 1.306–2.101, p < 0.001), whereas higher LMR values were protective (HR = 0.632, 95% CI: 0.514–0.777, p < 0.001). The RSF model demonstrated strong predictive accuracy (C-index: 0.985–0.986) and effectively stratified patients by survival risk. The CONUT score exerted the greatest prognostic influence, with the LMR providing additional discriminatory value. A gradual decline in survival probability was observed with an increasing CONUT score and a decreasing LMR. Conclusions: The application of machine learning to immune–nutritional data offers a robust tool for predicting survival in patients with advanced gastric cancer requiring HPN. This approach may enhance risk stratification, support individualised clinical decision-making regarding nutritional interventions, and inform treatment intensity adjustment. Full article

Background/Objectives: Operating rooms represent valuable and pivotal units of any hospital. Therefore, their management affects healthcare service delivery through rescheduling, staff shortage/overtime, cost inefficiency, and patient dissatisfaction, among others. To optimize scheduling, we aim to assess preoperative evaluation criteria that influence the prediction of surgery duration for gastric cancer (GC) patients. In GC, radical surgery with curative intent is the ideal treatment. Nevertheless, the intervention sometimes must be palliative if the patient’s status and tumor staging prove too advanced. Methods: A 6-year retrospective cohort study was performed in a tertiary care hospital, including all cases diagnosed with GC (ICD-10 code C16), confirmed through histopathology, and undergoing surgical treatment (N = 108). Results: The results of our study confirm male predominance (63.89%) among GC surgery candidates while bringing new perspectives on patient evaluation criteria and choice of surgical intervention (curative—Group 1, palliative—Group 2). Surgery duration, including anesthesiology (175.19 [95% CI (157.60–192.77)] min), shows a direct correlation with the number of lymph nodes dissected (Surgical duration [min] = 10.67 × No. of lymph nodes removed − 32.25). Interestingly, the aggressiveness of the tumor based on histological grade (highly differentiated being generally less aggressive than poorly differentiated) shows differential correlation with surgery duration among curative and palliative surgery candidates. Similarly, TNM staging indicates the need for a longer surgical duration (pTNM stage IIA, IIB, and IIIA) for curative interventions in patients with less advanced stages, as opposed to shorter surgery duration for palliative interventions (pTNM stage IIIC and IV). Conclusions: The study quantitatively presents the resources needed for the optimal surgical treatment of different groups of GC patients, as the disease coding systems in use regard the treatment of each pathology as “standard” in terms of patient management. The results obtained are anchored in the global perspectives of surgical outcomes and aim to improve the management of operating room scheduling, staff, and resources. Full article

Background: We investigated the possibility of predicting tumor burden with salivary extracellular RNA (exRNA) biomarkers in gastric cancer patients. Methods: Saliva samples were prospectively collected from 50 gastric cancer patients who underwent gastrectomy with curative intent. Approximately 5 mL of saliva was collected before surgery and on the 5th to 7th days after surgery. The expression of three mRNAs (SPINK7, PPL, and SEMA4B) and two miRNAs (miR140-5p and miR301a) that were previously validated was determined by reverse transcription quantitative real-time PCR. Results: There were significant differences in the pre-operative expression of PPL (p = 0.025), SEMA4B (p = 0.012), and miR140-5p (p = 0.036) between pathologic stage I/II and III/IV groups. The area under the curve (AUC) of each respective multivariable model in predicting stage III/IV, which was adjusted for age and sex, was 75.4% (PPL), 82.5% (SEMA4B), and 75.5% (miR140-5p). In the multivariable model, including all three biomarkers, the AUC was 89.2%. On the other hand, none of the conventional tumor markers (CEA, CA19-9, and CA72-4) could predict tumor burden before surgery. The AUC of the multivariable model, including CEA, CA19-9, and CA72-4, was 67.2%, 66.2%, and 67.4%, respectively. When all three tumor markers were included in the multivariable model, the AUC was 70.5%. Conclusions: Noninvasively detected salivary biomarkers have been shown to have higher diagnostic accuracy than conventional tumor markers detected by invasive blood tests for estimating pre-operative tumor burden. This study demonstrates the potential utility of these biomarkers in pre-operative risk assessment and monitoring surgical treatment response to gastric cancer. Full article

Background and Objectives: Gastric cancer (GC) remains a significant global health challenge with a poor prognosis. This study aimed to evaluate the association between Klintrup–Mäkinen (KM) inflammatory infiltrate grading and clinicopathological features in gastric cancer patients, investigating its potential as a prognostic marker. Material and Methods: This retrospective study analyzed 133 gastric adenocarcinoma patients diagnosed between 2020 and 2021 at County Clinical Hospital in Târgu Mureș, Romania. Patients were divided into two groups based on KM grades: low (grades 0–1, n = 62) and high (grades 2–3, n = 71). Clinicopathological characteristics and survival outcomes were compared between the groups. Results: Demographic characteristics were similar between the groups. Patients with low KM grades demonstrated significantly more aggressive tumor features, including a higher prevalence of Borrmann classification types III-IV (75.8% vs. 54.9%, p = 0.01), poorly differentiated histology (74.1% vs. 33.8%, p < 0.0001), advanced T stage (93.5% vs. 80.2%, p = 0.04), and lymph node involvement (87% vs. 60.5%, p = 0.0008). This group also exhibited higher rates of lymphatic invasion (79% vs. 50.7%, p = 0.001), venous invasion (51.6% vs. 30.9%, p = 0.02), perineural invasion (50% vs. 22.5%, p = 0.001), and positive surgical margins (32.2% vs. 15.4%, p = 0.02). Survival analysis revealed a hazard ratio of 1.642 (95% CI: 1.02–2.62) for patients with low KM grades compared to those with high KM grades. Conclusions: Low KM grades are associated with more aggressive tumor characteristics and poorer prognosis in GC patients. The KM score may serve as a valuable, cost-effective histological marker for assessing tumor aggressiveness and could aid in risk stratification when applied to routine H&E-stained slides. While it does not replace immunohistochemical or molecular analyses, integrating the KM score into pathological assessment may enhance prognostic accuracy and support identifying patients who might benefit from immunotherapy. 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

Peritoneal carcinomatosis is a common presentation found in advanced-stage gastrointestinal (GI) and gynecological cancers. Combined cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant survival benefits for select patients. CRS/HIPEC is not currently provided in Newfoundland and Labrador (NL). The Canadian HIPEC Collaborative Group recommends that centres complete a minimum of one case monthly to maintain competency and achieve good outcomes. Thus, we aimed to demonstrate that the annual patient volume in NL justifies the feasibility of implementing a combined surgical and gynecological oncology CRS/HIPEC program. Methods: A retrospective chart review of the NL Cancer Care Registry identified patients with stage IV colorectal, appendiceal, or gastric cancer and stage III to IV epithelial ovarian cancer over a 1-year period (1 January 2020–31 December 2020) to identify the number of patients meeting the criteria for CRS/HIPEC and/or those referred out of province to receive the treatment. The results are presented as proportions and percentages. Results: Thirty-one patients were eligible to receive CRS/HIPEC during the study period (11 GI, 20 gynecological). Of the GI patients, 63% were referred out of province for the procedure. Gynecological patients underwent CRS and systemic therapy +/− outpatient intraperitoneal chemotherapy in NL. Conclusions: Allowing patients to receive this standard of care treatment near home reduces financial, social, and emotional stressors. Our results confirm a sufficient patient volume to support a combined CRS/HIPEC program in NL. The implementation of this program will require multidisciplinary collaboration, specialized training, equipment, and protocol development. Full article

Gastric cancer is a significant global contributor to cancer-related mortality. Stage IV gastric cancer represents a significant percentage of patients in Western countries, with peritoneal dissemination being the most prevalent site. Peritoneal disease comprises two distinct entities, macroscopic (P1) and microscopic (P0CY1), which are associated with poor long-term survival rates. Although the present standard of treatment is palliative chemotherapy, a global controversy has arisen concerning specific patients with limited disease burden or conversion to negative lavage cytology following chemotherapy. Available approaches include systemic or intraperitoneal chemotherapy, upfront gastrectomy, and conversion surgery. This review consolidated the current evidence regarding multimodal management, indicating prolonged survival for this distinct subgroup of patients. Considering the complexity of peritoneal metastases, the potential of the multimodal approach unveils promising prospects for identifying the optimal treatment for this particular subset of stage IV patients and thus enhancing their survival outcomes. Full article

The management of chronic intestinal failure (CIF) secondary to advanced gastric cancer poses clinical challenges. This study explores the correlation between the Controlling Nutritional Status (CONUT) index and survival in patients with TNM stage IV gastric cancer on home parenteral nutrition (HPN). Methods: From 2015 to 2023, 410 patients (37% women, 63% men) with CIF due to advanced gastric cancer were assessed using CONUT scores, BMI, and biochemical tests. The Cox proportional hazards model was used to evaluate the impact of covariates on survival. Logistic regression categorized malnutrition levels by CONUT scores, with performance evaluated using precision, recall, and F1 scores. A p-value < 0.001 was statistically significant. Results: The CONUT scores were independent predictors of survival, with higher CONUT scores increasing mortality risk (HR = 2.073, 95% CI: 1.815–2.369, p < 0.001). The model achieved an overall accuracy of 71%, indicating correct classification for the majority of cases. Conclusions: CONUT scores are key predictors of survival in patients receiving HPN for CIF due to stage IV gastric cancer. Full article

Background and Objectives: Temperature-sensitive (TS) mutants of TP53 are thermally unstable, unfolded, and inactive at body temperature but can be refolded and reactivated at sub-physiological temperatures. TS TP53 may be amenable for functional rescue by hypothermia or structure-stabilizing drugs, and may retain low-level transcriptional activity at 37 °C. TP53 mutations are observed in 47% of all esophageal cancers (ECs) and 25% to 40% of gastric cancers (GCs). We aimed to investigate the trends and outcomes of EC and GC with TS TP53 mutations using cBioportal. We hypothesize that TS TP53 mutants in EC and GC present a unique prognostic profile distinct from non-TS TP53 mutants, potentially affecting overall survival and cancer progression. Materials and Methods: We identified 1924 patients from cBioportal with GC or EC, harboring any TP53 mutation. Patients were then stratified based on the TP53 temperature sensitivity according to a recently reported functional analysis of its activity. Patients were also stratified based on a history of Barrett’s esophagus (BE), cancer stage, sex, and race. We then compared populations (TS vs. non-TS TP53) to assess differences and evaluated survival outcomes. Results: Males represented 77% of the cohort, and 51.6% of the samples were from patients with stage IV cancer. No association was found between TS vs. non-TS mutational status and BE, cancer stage, or race. Interestingly, a significantly higher proportion of females (22.9%) than males (14.5%) displayed a TS TP53 mutation (p = 0.012). No significant difference was seen in overall survival between the TS and non-TS mutations capable of ≥50% growth suppression at 32 °C (median = 33 vs. 28 months, p = 0.36). This trend was also observed when the patients were filtered based on cancer location. The median survival for EC was 32.5 months compared to 33 months (p = 0.67). In cases of GC, median survival times could not be determined due to the insufficient number of events. Conclusions: Although no statistical significance was observed, a decrease in overall survival for patients with TS TP53 mutations was noted. The result is counterintuitive given that TS mutants have less severe structural destabilization and suggests TS TP53 mutations may have a unique prognostic value that warrants further investigation. Full article

Background: Less than 25% of gastric cancers (GC) are discovered early, leading to limited treatment options and poor outcomes (27.8% mortality, 3.7% 5-year survival). Screening programs have improved cure rates, yet post-diagnosis treatment guidelines remain unclear (systemic chemotherapy versus surgery). The optimal type of palliative surgery (palliative gastrectomy (PG), surgical bypass (SB), endoscopic stenting (ES)) for long-term outcomes is also debated. Methods: A literature review was conducted using PubMed, MEDLINE, and EMBASE databases along with Google Scholar with the search terms “gastric cancer” and “palliative surgery” for studies post-1985. From the initial 1018 articles, multiple screenings narrowed it to 92 articles meeting criteria such as “metastatic, stage IV GC”, and intervention (surgery or chemotherapy). Data regarding survival and other long-term outcomes were recorded. Results: Overall, there was significant variation between studies but there were similarities of the conclusions reached. ES provided quick symptom relief, while PG showed improved overall survival (OS) only with adjuvant chemotherapy in a selective population. PG had higher mortality rates compared to SB, with ES having a reported 0% mortality, but OS improved with chemotherapy across both SB and PG. Conclusions: Less frail patients may experience an improvement in OS with palliative resection under limited circumstances. However, operative intervention without systemic chemotherapy is unlikely to demonstrate a survival benefit. Further research is needed to explore any correlations. Full article

Gastric cancer (GC) with peritoneal carcinomatosis (PC) has a particularly unfavorable prognosis. This limited survival raises doubts about which factors confer an extremely worse outcome and which patients could benefit from more aggressive treatments, in an attempt to improve survival and better control the disease. This study aimed to evaluate the survival outcomes of patients with PC due to GC and develop a prognostic score to predict 6-month mortality. We performed an analysis of clinical stage IV GC with PC. Scores were assigned to risk factors and calculated for each patient from nine variables. Among 326 IVB GC, 211 (64.7%) had PC and were included. After calculating the score, 136 (64.5%) GCs were classified as a low-risk group and 75 (35.5%) as a high-risk group. Median OS was 7.9 and 1.9 months for low- and high-risk patients (p < 0.001). In the high-risk group, 77.3% of the patients died in <6 mo (p < 0.001). Palliative surgery and chemotherapy were associated with better survival, and the prognostic groups maintained statistical significance even when the same type of treatment was performed. In conclusion, the scoring system developed with variables related to patient performance status and clinical data was able to distinguish GC with PC with a high risk of 6-month mortality. Accordingly, verifying and validating our findings in a large cohort of patients is necessary to confirm and guarantee the external validation of the results. Full article

Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13–106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13–18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival. Full article

(1) Background: The aim of our study was to assess the involvement of the sympathetic nervous system in the progression of patients with gastric carcinoma by analyzing the sympathetic neuronal fibers and beta 2 adrenoreceptors. (2) Methods: We performed a retrospective study in which we analyzed the clinical, biological, and histological data from a total of 104 patients diagnosed with stomach cancer. (3) Results: After analyzing the immunoreactivity of beta 2 adrenoreceptors, we observed increased values in patients with tumors larger than 5 cm in diameter (p = 0.0371), with a deeper degree of tumor invasion T3–4 (p = 0.0159), invasion in more than two lymph nodes (p = 0.0462), or a TNM stage III–IV. Regarding the survival analysis, better survival rates (65%) were observed for patients with a low value of beta 2 adrenoreceptors (B2A−), compared to B2A (+) patients, in which survival at 3 years of follow-up was only 43%. In addition, the analysis of intra-tumoral sympathetic fibers showed a better survival rate (83%) for patients with a low value of density compared to patients with increased density, in whom the survival rate was only 24%. (4) Conclusions: The findings of this study indicate that patients with stomach cancer have a more unfavorable prognosis when they have a higher density of sympathetic nerve fibers and an increased expression of beta 2 adrenergic receptors inside the tumor. Full article

Recent advances in our understanding of gastric cancer biology have prompted a shift towards more personalized therapy. However, results are based on population-based survival analyses, which evaluate the average survival effects of entire treatment groups or single prognostic variables. This study uses a personalized survival modelling approach called individual survival distributions (ISDs) with the multi-task logistic regression (MTLR) model to provide novel insight into personalized survival in gastric adenocarcinoma. We performed a pooled analysis using 1043 patients from a previously characterized database annotated with molecular subtypes from the Cancer Genome Atlas, Asian Cancer Research Group, and tumour microenvironment (TME) score. The MTLR model achieved a 5-fold cross-validated concordance index of 72.1 ± 3.3%. This model found that the TME score and chemotherapy had similar survival effects over the entire study time. The TME score provided the greatest survival benefit beyond a 5-year follow-up. Stage III and Stage IV disease contributed the greatest negative effect on survival. The MTLR model weights were significantly correlated with the Cox model coefficients (Pearson coefficient = 0.86, p < 0.0001). We illustrate how ISDs can accurately predict the survival time for each patient, which is especially relevant in cases of molecular subtype heterogeneity. This study provides evidence that the TME score is principally associated with long-term survival in gastric adenocarcinoma. Additional external validation and investigation into the clinical utility of this ISD model in gastric cancer is an area of future research. Full article