Endoscopic Full-Thickness Resection for Gastrointestinal Lesions: Current Evidence and Clinical Practice

Abstract

Endoscopic full-thickness resection (EFTR) has emerged as a novel, minimally invasive therapeutic modality for the management of select gastrointestinal (GI) lesions that are not amenable to conventional endoscopic resection techniques. This review synthesizes current scientific evidence, recent guideline recommendations, and expert clinical insights on EFTR, focusing on its indications, mechanisms, clinical outcomes, safety profile, and future prospects in the management of complex GI lesions. The discussion highlights the epidemiology of target lesions, pathophysiological rationale for full-thickness resection, patient selection criteria, diagnostic approach, and technical considerations, while emphasizing the clinical impact of recent advances and ongoing research in the field.

Introduction

Gastrointestinal lesions, including subepithelial tumors, non-lifting adenomas, and early cancers, often pose significant diagnostic and therapeutic challenges, particularly when traditional endoscopic resection techniques such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are insufficient or technically unfeasible. EFTR is an innovative endoscopic technique that allows for the en bloc removal of lesions involving all layers of the GI wall, thereby expanding the therapeutic frontier for lesions previously managed surgically. This article provides an in-depth review of EFTR, integrating recent clinical trial data, mechanistic understanding, and expert perspectives to delineate its role in contemporary GI endoscopy practice.

Epidemiology / Disease Burden

The global incidence of GI tract neoplasms and complex polyps continues to rise, reflecting advances in screening and diagnostic endoscopy. Subepithelial tumors, such as gastrointestinal stromal tumors (GISTs), and non-lifting colorectal adenomas constitute a significant subset of lesions encountered in routine practice. Approximately 10-15% of colorectal polyps are non-lifting due to submucosal fibrosis or prior interventions, rendering them challenging for EMR or ESD. Similarly, subepithelial lesions are detected in up to 0.5% of upper GI endoscopies. The burden of surgical resections for benign or indeterminate lesions remains considerable, underscoring the need for minimally invasive alternatives like EFTR.

Pathophysiology

Lesions requiring full-thickness resection often involve the muscularis propria or display submucosal fibrosis, as seen in scarred adenomas, neuroendocrine tumors, and certain early-stage cancers. The inability to achieve en bloc resection with traditional methods increases the risk of incomplete excision and local recurrence. EFTR addresses this by enabling controlled resection through all layers of the GI wall, including the serosa, thereby ensuring complete histological clearance and facilitating accurate pathological staging, which is pivotal for oncological management.

Risk Factors

Risk factors for lesions necessitating EFTR include prior endoscopic interventions leading to fibrosis, lesion morphology (non-lifting, sessile, or subepithelial), and location in anatomically challenging sites such as the appendiceal orifice, ileocecal valve, or duodenum. Genetic syndromes like familial adenomatous polyposis and Peutz-Jeghers syndrome may increase the prevalence of complex polyps requiring advanced resection techniques. Additionally, patient comorbidities and anticoagulation status influence procedural planning and risk assessment.

Clinical Features

Patients with GI lesions amenable to EFTR are frequently asymptomatic, with lesions detected incidentally during surveillance or screening endoscopy. Symptomatic presentations may include occult GI bleeding, anemia, or, less commonly, obstruction. Subepithelial tumors may present as subtle protrusions with normal overlying mucosa, while non-lifting adenomas can be visualized as flat or sessile polyps resistant to conventional lifting techniques. Careful endoscopic characterization, including assessment of size, morphology, and involvement of deeper layers, is essential for appropriate selection.

Diagnosis

Accurate diagnosis involves a combination of high-definition endoscopic imaging, chromoendoscopy, and adjunctive modalities such as endoscopic ultrasound (EUS) for subepithelial lesions. EUS delineates the layer of origin, vascularity, and relationship of the lesion to adjacent structures, which is critical for procedural planning. Biopsy may be limited for subepithelial lesions, necessitating en bloc resection for definitive histopathological diagnosis. Cross-sectional imaging is reserved for staging when malignancy is suspected.

Treatment & Management

EFTR is indicated for lesions not amenable to EMR or ESD, including non-lifting adenomas, small subepithelial tumors, and select early-stage cancers without high-risk features for lymphatic spread. The procedure can be performed using dedicated devices such as the full-thickness resection device (FTRD), which integrates an over-the-scope clip (OTSC) and snare system. The technique involves lesion marking, clip deployment to close the resection site, followed by snare excision, thereby minimizing the risk of perforation. Post-procedural care includes monitoring for adverse events such as bleeding, perforation, or infection. Multidisciplinary input is essential for cases with malignant potential.

Recent Advances / Emerging Therapies

Recent innovations in EFTR include the development of novel resection devices, improved closure techniques, and integration of real-time imaging modalities to guide resection and confirm completeness. Hybrid approaches combining ESD and EFTR have shown promise in expanding indications and improving outcomes. Data from multicenter registries and prospective studies suggest high rates of technical success (85-95%) and R0 resection (70-90%), with acceptable complication rates. Ongoing trials are evaluating EFTR in the management of early GI cancers and as a platform for translational research, such as organoid-based personalized treatments.

Guideline Recommendations

International guidelines from the European Society of Gastrointestinal Endoscopy (ESGE) and American Society for Gastrointestinal Endoscopy (ASGE) recognize EFTR as an option for select lesions unamenable to standard endoscopic resection. Key recommendations include careful patient selection, use of dedicated devices, and performance in high-volume centers with multidisciplinary support. Guidelines emphasize the importance of informed consent, detailed procedural planning, and post-resection surveillance, particularly in cases with malignant or indeterminate pathology.

Conclusion

EFTR represents a paradigm shift in the management of challenging GI lesions, offering a minimally invasive alternative to surgery with high rates of technical and clinical success. Its utility in achieving complete resection of non-lifting adenomas and subepithelial tumors is well-supported by recent evidence. Ongoing research and technological refinement are expected to expand its indications and improve safety. Optimal outcomes are contingent on rigorous patient selection, operator expertise, and adherence to guideline-based protocols, positioning EFTR as an essential tool in the armamentarium of therapeutic endoscopy.