Endoscopic management of NVNPUB - A Canadian Guideline

The Canadian Association of Gastroenterology (CAG), in collaboration with international experts, has developed evidence-based guidelines specifically for the endoscopic management of nonvariceal, nonpeptic ulcer upper gastrointestinal bleeding (NVNPUB). This guideline addresses bleeding caused by conditions such as malignant tumors, Mallory-Weiss tears (MWTs), Dieulafoy’s lesions (DLs), and gastric antral vascular ectasia (GAVE). Below is a detailed overview of the guidelines:

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### **Purpose**

The guideline provides recommendations to standardize the management of NVNPUB, which has seen an epidemiologic shift in recent years. NVNPUB now accounts for one-third to two-thirds of upper gastrointestinal (GI) bleeding cases, surpassing peptic ulcer bleeding due to a decline in ulcer incidence and a rise in malignancy and vascular-related causes.

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### **Development and Methodology**

• **Origin**: Developed by the CAG with international collaboration and endorsed by major societies such as the American Gastroenterological Association (AGA), American Society for Gastrointestinal Endoscopy (ASGE), European Society of Gastrointestinal Endoscopy (ESGE), and World Endoscopy Organization (WEO).
• **Framework**: Recommendations were formed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, which evaluates evidence strength and balances benefits against risks.
• **Recommendation Classification**: Recommendations are categorized as either strong ("panel recommends") or conditional ("panel suggests") based on the certainty of evidence and balance of effects.

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### **Key Recommendations for Endoscopic Management**

#### **1. Malignant Upper GI Bleeding**

• **Preferred Treatment**: The guidelines suggest using topical hemostatic agents (THAs) over conventional endoscopic therapy or no therapy. THAs are associated with better hemostasis and fewer rebleeding events, though the evidence supporting this is of very low certainty.
• **Evidence**: TC-325 powder (a THA) demonstrated a lower further bleeding rate (26%) compared to standard therapy (50%), with immediate hemostasis failure in 5% of cases and a 2% adverse event rate.
• **Conventional Therapy**: Mechanical methods (e.g., clips), thermal methods (e.g., argon plasma coagulation [APC], bipolar electrocoagulation), and injection therapies (e.g., epinephrine, sclerosants) remain viable but are less effective for diffusely oozing tumors.
• **Oncologic Therapy**: Following endoscopic hemostasis, oncologic treatments such as surgery, chemotherapy, or radiation are recommended when feasible. These interventions improve six-month survival rates despite higher toxicity risks.

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#### **2. Mallory-Weiss Tears (MWTs)**

• **Active Bleeding**: For spurting or oozing bleeding, endoscopic therapy using endoscopic band ligation (EBL) or through-the-scope clips (TTSC) is recommended over epinephrine injection or no therapy.
• **Nonbleeding Stigmata**: For nonbleeding stigmata, the guidelines suggest against intervention.

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#### **3. Dieulafoy’s Lesions (DLs)**

• **Preferred Treatment**: Mechanical methods such as EBL or TTSC, or contact thermal coagulation, are preferred over epinephrine injection alone.
• **Discouraged Therapy**: Epinephrine injection alone is strongly discouraged due to high rebleeding rates.

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#### **4. Gastric Antral Vascular Ectasia (GAVE)**

• **Preferred Treatment**: EBL is suggested over APC due to better outcomes, including fewer transfusion requirements and greater hemoglobin improvement.

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### **Adverse Events**

Endoscopic therapies generally have low complication rates. For topical hemostatic agents, adverse effects occur in approximately 2% of cases, mostly presenting as mild distension or bleeding.

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### **Research Gaps**

The guideline highlights the need for randomized controlled trials (RCTs) comparing THAs with conventional or combined therapies. Additional research is needed to evaluate patient-reported outcomes, cost-effectiveness, and quality of life in NVNPUB management.

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### **Outcome Priorities**

Critical outcomes considered in the guidelines include:

• Further bleeding
• Rebleeding rates
• Hemostasis success
• Transfusion requirements
• Mortality within 7–30 days

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### **Certainty of Evidence**

Most recommendations are conditional and based on very low certainty due to limited RCTs and heterogeneity in study designs and populations.

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### **Equity and Feasibility**

The accessibility of THAs may pose challenges in low-resource settings. The guidelines emphasize equitable implementation strategies to ensure widespread applicability.

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### **Patient-Centered Approach**

The guidelines encourage shared decision-making tailored to patient-specific factors, such as:

• Comorbidities
• Severity of bleeding
• Treatment goals (comfort vs. aggressive therapy)

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### **Implementation Value**

This guideline offers a global framework for NVNPUB management, aiming to standardize care, improve patient outcomes, and guide local adaptations by healthcare systems. It serves as a critical tool for clinicians managing upper GI bleeding from nonvariceal, nonpeptic ulcer causes.

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In summary, the Canadian guideline for NVNPUB management emphasizes the use of topical hemostatic agents for malignant bleeding, mechanical methods for MWTs and DLs, and endoscopic band ligation for GAVE. It prioritizes patient-centered care and highlights areas for future research to address evidence gaps.