Abstract
Objective
We aimed to investigate whether the presence of bleeding complaints at initial presentation affected laboratory and histopathological features in patients diagnosed with gastric cancer, dividing the patients into two groups: those with and those without such complaints.
Methods
Data from 148 patients diagnosed with gastric cancer were retrospectively analyzed using the hospital’s computerized medical record system. Patients were grouped based on the presence or absence of hematemesis or endoscopic signs of bleeding, and compared with respect to age, sex, tumor location, disease stage, hemogram parameters, neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV)-to-platelet ratio (PLT), and blood group characteristics. Tumors located in the fundus or cardia were classified as proximal gastric tumors. Non-parametric variables were analyzed using the Mann-Whitney U test, parametric variables were analyzed using the independent samples t-test, and categorical variables were analyzed using the chi-square test. A p-value of ≤0.05 was considered statistically significant.
Results
Among the 148 patients included in the study (median age: 61.09 years; range: 29-87 years), 67 presented with bleeding symptoms, while 81 did not. There was no statistically significant difference in age or sex distribution between the two groups. Tumor localization, histological subtype, disease stage, and blood group characteristics were also similar between groups. Although the hemoglobin levels were lower in the bleeding group, this difference was not statistically significant (p=0.352). However, neutrophil counts were significantly higher (p=0.020) and lymphocyte counts significantly lower (p=0.007) in patients with bleeding. No significant differences were observed in platelet count, MPV, NLR, or MPV/PLT. The presence of bleeding was not associated with the need for neoadjuvant chemotherapy (p=0.155).
Conclusion
The presence of bleeding at initial presentation in patients with gastric cancer was not associated with differences in demographic features, tumor localization, histopathological subtype, or clinical stage. However, altered neutrophil and lymphocyte counts suggest that the bleeding may indicate an acute inflammatory response. These findings highlight the potential role of hematologic parameters as adjunctive markers in the initial assessment of gastric cancer patients presenting with gastrointestinal bleeding.
Introduction
Gastric cancer ranks as the fifth most common malignancy worldwide(1). Its clinical presentation is highly variable, and a significant proportion of patients are diagnosed at an advanced stage. While most patients present with non-acute constitutional symptoms such as weight loss, abdominal pain, and fatigue, gastric cancer may also manifest with acute complications including hematemesis, tumor or organ perforation, or gastric outlet obstruction-conditions that have been associated with poor overall survival(2, 3). In fact, the overall survival of patients presenting with such acute symptoms has been reported to be as short as six months(4). However, improved diagnostic tools and advancements in treatment have contributed to better overall survival rates in recent years.
Bleeding due to malignancy accounts for approximately 3% of upper gastrointestinal (GI) bleeding cases(5). Regardless of etiology, upper GI bleeding is associated with a mortality rate ranging from 2% to 10%(6). Although bleeding is a significant clinical feature of gastric cancer, it is not always evident. Some patients present with overt symptoms such as hematemesis or melena, whereas others have minor bleeding confirmed only by microcytic anemia or show no signs of bleeding.
This study aims to compare the clinical and pathological characteristics of gastric cancer patients based on the presence or absence of bleeding at the time of initial presentation. The findings are expected to enhance our understanding of the diverse clinical manifestations of gastric cancer and contribute to the development of improved diagnostic and therapeutic strategies.
Materials and Methods
The study was approved by the Ethics Committee of University of Health Sciences Türkiye, İzmir Tepecik Education and Research Hospital (approval no: 2025/05-23, date: 12.06.2025). Given the retrospective design, the requirement for informed consent was waived.
This was a retrospective, single-center cohort study conducted between 2011 and 2023. A total of 148 consecutive patients diagnosed with gastric cancer during this period were included. Patients with prior gastric surgery affecting bleeding risk, hematologic disorders that could alter laboratory parameters, or incomplete clinical data were excluded.
Patients were stratified into two groups based on their bleeding status at initial presentation. The bleeding group included patients presenting with hematemesis, melena, or endoscopic evidence of bleeding. The non-bleeding group consisted of patients who had no clinical or endoscopic signs of upper GI bleeding at diagnosis.
Data were extracted from the hospital’s electronic medical records, including several key variables. Demographic data included age, sex, and blood group. Tumor characteristics included location (categorized as proximal-cardia/fundus/corpus-, or antrum), histopathology, and clinical stage according to the American Joint Committee on cancer tumor node metastasis classification. Laboratory parameters at presentation were recorded, including hemoglobin, leukocyte count, neutrophil count, lymphocyte count, platelet count, mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and MPV-to-platelet ratio (PLT). Treatment data included whether patients received neoadjuvant chemotherapy.
Statistical Analysis
Statistical analyses were performed using IBM SPSS Statistics, version 20 (IBM Corp., Armonk, NY, USA). Normality was assessed with the Kolmogorov-Smirnov test. Normally distributed variables were reported as mean ± standard deviation and compared using the independent samples t-test. Non-normally distributed variables were presented as medians (interquartile ranges) and compared with the Mann-Whitney U test. Categorical variables were analyzed using the chi-square test or Fisher’s exact test as appropriate. A p-value ≤0.05 was considered statistically significant.
Results
A total of 148 patients aged 29-87 years were included in the study; the median age was 61.09 years. Among the 67 patients who presented with GI bleeding (age range 37-84 years), the mean age was 61.18 years; among the 80 patients without bleeding (age range 29-87 years), the mean age was 61.01 years. According to the Kolmogorov-Smirnov test, the age distributions in both groups were normal. When patients were stratified using age thresholds of ≥50, ≥60, and ≥70 years, no statistically significant association was found between age and bleeding at presentation (p=0.767, p=0.305, and p=0.540, respectively).
Of the 148 patients, 64% were male (n=95) and 36% were female (n=53). There was no significant difference in sex between patients with bleeding at diagnosis and those without (p=0.732). Tumor histopathology was also similar between the two groups (Table 1).
Regarding blood types, 35.2% of patients were blood group 0, 47.7% group A, 8.6% group B, and 8.6% group AB. No significant association was found between blood group and the presence of bleeding (p=0.556). Additionally, no significant differences were observed according to the presence of A or B antigens or antibodies (p=0.947 and p=0.179, respectively).
Tumor localization was as follows: corpus (41.2%), antrum (35.8%), and proximal stomach (fundus and/or cardia) (23%). Tumor location did not differ significantly between the bleeding and non-bleeding groups (p=0.403) (Figure1).
The presence of metastasis at diagnosis did not differ significantly between groups (p=0.056).
When hematological parameters were compared, the median leukocyte count was significantly higher in patients presenting with bleeding (p=0.001), and the neutrophil count was also significantly elevated in this group (p=0.035). The median lymphocyte count tended to be lower in bleeding patients (p=0.007). However, there was no significant difference in hemoglobin (p=0.601), platelet count (p=0.607), MPV (p=0.274), NLR (p=0.118), or MPV-to-PLT (p=0.324) between the two groups.
Lymphocyte count was normally distributed in non-bleeding patients, with a median of 1.90 x109/L; in bleeding patients it was non-normally distributed, with a median of 1.50 x109/L (p=0.025) (Table 2).
Histopathological evaluation of surgical specimens revealed no significant difference in tumor type between groups (p=0.877) (Table 3).
Among patients who received neoadjuvant chemotherapy, 45.5% were in the bleeding group and 54.5% in the non-bleeding group; this difference was not statistically significant (p=0.155).
Discussion
In this retrospective study, clinical and laboratory parameters of patients diagnosed with gastric cancer were compared between those with and those without bleeding symptoms at initial presentation. Although hemoglobin levels were lower in patients presenting with bleeding, this difference did not reach statistical significance. This may be attributed to the acute or chronic nature of the bleeding, the hemodynamic stability of the patients, or the extent of blood loss. Additionally, the limited sample size may have contributed to the lack of statistical significance. While some studies have reported a higher incidence of GI bleeding among males and older patients, our findings did not confirm this association(7).
Inflammation is increasingly recognized as both an initiator and a promoter of cancer pathogenesis. Biological mediators released during the inflammatory process can cause structural damage to DNA, inhibit apoptosis, and facilitate tumor cell proliferation and metastasis. Consequently, inflammatory markers have been widely investigated in various types of cancer in recent years(8, 9). Among these, neutrophil, lymphocyte, and platelet counts, as well as ratios such as NLR and MPV-to-PLT, have been frequently evaluated.
In patients presenting to emergency departments with non-malignant upper GI bleeding, higher NLRs have been associated with increased mortality, whereas hemoglobin and hematocrit levels, leukocyte and platelet counts, and MPV were not significantly correlated with mortality(10). However, no well-established thresholds or values have been defined specifically for bleeding attributable to gastric cancer. In our study, significantly elevated neutrophil counts and reduced lymphocyte levels in the bleeding group may reflect an acute inflammatory response to tumor-induced mucosal injury or suggest processes such as microbial translocation. Previous research has shown that lymphocyte counts-indicators of key players in the anti-tumor immune response-are often reduced in cancer patients(11).
Bleeding may result not only from tumor characteristics but also from acquired or iatrogenic causes. Major risk factors for GI bleeding include Helicobacter pylori infection, non-steroidal anti-inflammatory drug use, stress, and gastric acid secretion(12). In this study, these factors were not assessed, and bleeding was analyzed only in relation to tumor histology and stage.
We found no significant association between bleeding and tumor localization, histological subtype, tumor stage, or demographic characteristics such as age and sex. This suggests that bleeding in gastric cancer may not depend solely on anatomical or histological features, but may involve more complex biological mechanisms. Previous studies have similarly reported no strong correlation between tumor location and bleeding in gastric cancer patients.
Study Limitations
This study has several limitations. Firstly, its retrospective, single-center design limits the generalizability of the findings. Furthermore, bleeding severity was not graded, and distinguishing acute from chronic bleeding was not possible, complicating the interpretation of the results. The standardization of laboratory tests and the timing of measurements, particularly the reliance on initial hemogram values at admission, may also have influenced the findings. Lastly, other genetic or iatrogenic factors that may predispose to bleeding were not assessed and could be explored in future research.
Conclusion
In this retrospective study, the presence of GI bleeding at initial presentation in patients with gastric cancer was not associated with significant differences in demographic characteristics, tumor location, histopathological subtype, or clinical stage. However, significantly elevated neutrophil counts and decreased lymphocyte levels in the bleeding group suggest an acute inflammatory response potentially linked to tumor-related mucosal injury. These findings underscore the potential utility of hematological parameters, particularly neutrophil and lymphocyte counts, as adjunctive markers in the early evaluation of gastric cancer patients presenting with bleeding. Further prospective studies are warranted to validate these associations and explore their prognostic implications.
