Endoscopic Application of Tranexamic Acid and Sucralfate in Gastrointestinal Tumor Bleeding: A Randomized Controlled Trial

Upper gastrointestinal (GI) cancer bleeding is a challenging scenario in clinical practice, including esophageal cancer, gastric cancer, and duodenal cancer. Upper GI cancer bleeds because the growing tumor erodes into the gastrointestinal lining and blood vessels, creating ulcers or damaging capillaries. Certain risk factors contribute to upper GI tumor bleeding, including advanced tumor stage, male gender, older age, usage of certain medications (NSAIDs, anticoagulants, antiplatelets), and comorbidities like thrombocytopenia, coagulopathy, and chronic kidney disease.

Furthermore, angiogenesis in upper GI tumors increased the fragility of new tumor blood vessels, leading to slow oozing or severe hemorrhage. Upper GI cancer exosomes play a significant role in gastric cancer progression, influencing metastasis, drug resistance, and the tumor microenvironment. Exosomes contain and transport a wide range of DNA, mRNA, and miRNA molecules. Tumor-derived exosomes carry pro-angiogenic factors like vascular endothelial growth factor (VEGF) and miR-21, enhancing vessel permeability and clot instability in bleeding sites. In tumors, VEGF drives pathological angiogenesis, enabling tumor growth, invasion, and metastasis by forming leaky vessels. VEGF is transported via exosomes, leading to GI tumor bleeding risks. High serum VEGF also correlates with poor prognosis in gastric cancers. MiR-21 acts as an oncomiR in tumors, overexpressed across many cancers to promote proliferation, invasion, and metastasis by targeting tumor suppressor genes. In gastric cancers, elevated miR-21 correlates with advanced stages, angiogenesis, and bleeding risks through vessel instability.

Gastrointestinal tumor bleeding represents approximately 3-5% of all gastrointestinal bleeding cases, posing significant clinical challenges due to its unique pathophysiology and treatment complexity. The management of such bleeding is particularly difficult because malignant lesions have distinct characteristics compared to benign etiologies of bleeding. Gastrointestinal tumors often exhibit invasive growth patterns, causing disruption of the normal tissue architecture. They frequently develop multiple ulcerations on their surface, which serve as persistent bleeding sites. Additionally, local blood vessels within or adjacent to the tumor can be damaged or fragile, further complicating hemostasis.

In this situation, conventional endoscopic treatment, such as epinephrine injection, clipping, or heat coagulation for tumor bleeding, is challenging and less effective. Cohort studies have reported initial endoscopic hemostasis rates ranging from 31% to 86%, with rebleeding rates between 28% and 80% when using conventional endoscopic hemostatic methods. Hemostatic powder spray, introduced in clinical practice since around 2011, represents a novel endoscopic technique for managing active GI bleeding. The hemostatic powder is delivered through a spraying system under endoscopic visualization. When applied to the bleeding site, the hemostatic powder absorbs water and swells to create an adhesive barrier that covers the lesion and promotes hemostasis. Hemospray has been proven to achieve immediate hemostasis and decrease 30-day rebleeding rates in gastrointestinal tumor bleeding. However, current hemostatic powders on the market are expensive, and some case reports have indicated a risk of perforation in the gastrointestinal tract associated with Hemospray.

Tranexamic acid (TXA) is a well-known antifibrinolytic agent that inhibits fibrin degradation by binding to tissue plasminogen, thereby preventing blood clot lysis and reducing bleeding. Our recent study evaluating the effect of topical TXA powder on bleeding peptic ulcers demonstrated that the precise endoscopic administration of TXA powder can enhance the stop-bleeding effect. This study involved 60 patients (30 in each group) with peptic ulcer bleeding. The application of topical TXA reduced the early treatment failure rate (6.7% vs 30%, P = 0.042).