2024 Chinese expert consensus on clinical utilization of laparoscopic and endoscopic cooperative surgery for gastric tumors

Introduction Gastric tumors represent a significant subset of gastrointestinal pathologies. Among these, gastric cancer is the most common malignancy, ranking fifth in global incidence and third in cancer-related mortality within China.[1] The increasing adoption of endoscopic procedures has contributed to an increasing annual rate of early gastric cancer (EGC).[2–3] Additionally, gastric submucosal tumors (SMTs), which are primarily composed of stromal tumors and leiomyomas, originate from protruding lesions in the nonmucosal layer and are being detected with increasing frequency.[4] Surgical intervention remains the preferred treatment for gastric tumors. Advances in laparoscopic and endoscopic techniques have facilitated the widespread adoption of minimally invasive surgical approaches in China. While laparoscopic surgery and digestive endoscopy each have inherent limitations, their integration combines complementary strengths, paving the way for the development of less invasive, more precise, and function-preserving treatment modalities for gastric tumors. This consensus has been formulated to standardize the clinical application of laparoscopy-endoscopy cooperative surgery (LECS) for the management of gastric tumors. The objective is to provide a scientific framework and practical guidance to ensure the safe and effective implementation of LECS in clinical practice. All the recommendations in this document were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, which categorizes evidence quality into four levels (A, B, C, and D) [Supplementary Table 1, https://links.lww.com/CM9/C553] and classifies the recommendations as either strong or weak. Current Status and Clinical Potential The widespread implementation of laparoscopy and digestive endoscopy for managing gastric tumors has significantly expanded minimally invasive treatment options. Nevertheless, both modalities present distinct limitations. Endoscopic therapy alone may result in noncurative resections, particularly for large or deeply invasive tumors. Moreover, complications such as perforation and bleeding associated with endoscopic therapy can pose substantial challenges to management. Conversely, laparoscopic surgery is often ineffective for the localization of EGC or small intrinsic tumors given the absence of direct mucosal surface visualization. In cases of EGC, overly aggressive laparoscopic interventions and the subsequent need for gastrointestinal reconstruction may lead to complications such as anemia and gastroesophageal reflux. The advent and evolution of multidisciplinary approaches have augmented the synergistic application of laparoscopy and digestive endoscopy, yielding notable advantages and practical utility in the management of gastric tumors. This integration represents a paradigm shift in the innovative application of medical and surgical technologies for gastrointestinal diseases. LECS has emerged as a transformative modality in the treatment of gastric tumors. LECS not only extends the applicability of endoscopic and laparoscopic techniques but also enhances surgical precision, minimizes patient trauma, and adheres to principles of organ and functional preservation. These attributes render LECS a promising strategy for personalized, minimally invasive treatment protocols with substantial clinical potential. Recommendation 1: The combined use of laparoscopy and digestive endoscopy represents a minimally invasive, individualized, and multidisciplinary approach that provides precise diagnostic and therapeutic options for patients with gastric tumors. (Quality of evidence: B; strength of recommendation: strong; level of consensus: 100% agreement). Applications During laparoscopic surgery for gastric tumors, the integration of intraoperative endoscopy plays a critical role in accurately assessing tumor location and size, thereby optimizing the extent of laparoscopic resection.[5] This approach facilitates real-time evaluation of anastomoses, significantly reducing the incidence of postoperative complications. LECS has broadened the indications for surgical intervention, including SMTs located in anatomically challenging regions, such as the gastroesophageal junction and pylorus, as well as EGC with high-risk features for endoscopic resection or potential lymph node metastasis. This integrated approach enhances the precision and safety of surgical procedures, ensures optimal surgical outcomes, minimizes operative trauma, and improves postoperative quality of life.[6–7] Recommendation 2: The combined use of laparoscopy and digestive endoscopy is strongly recommended for tumor localization and marking, tumor excision, and anastomotic assessment to enhance surgical quality control and patient safety. (Quality of evidence: B; strength of recommendation: strong; level of consensus: 100% agreement). Utilization of Endoscopy in Laparoscopic Surgeries for Gastric Tumors Utilization of endoscopy in the assessment and localization of gastric tumors The accurate localization of small gastric tumors during laparoscopic procedures poses significant challenges; however, intraoperative endoscopy facilitates precise tumor localization and marking. By employing intraoperative digestive endoscopy, surgeons can determine the nature and extent of lesions, while magnifying endoscopy offers a more precise delineation of EGC boundaries, enabling accurate determination of resection margins.[8] The endoscopic submucosal injection of contrast agents assists in lesion identification from the serosal surface during surgery and supports tracing the sentinel node basin (SNB).[9–10] Commonly used markers for endoscopic tumor labeling include carbon nanoparticle suspension (CNS) and indocyanine green (ICG) fluorescence.[11–12] However, their application may be limited by contrast agent diffusion, which can compromise margin accuracy. Preoperative endoscopic placement of titanium clips, combined with intraoperative endoscopic confirmation, provides effective demarcation of tumor boundaries, ensuring procedural efficiency.[13–14] Neoadjuvant therapy is increasingly employed as a strategic approach for advanced gastric cancer, inducing regression of lesions and tumor downstaging. However, it may complicate tumor localization and boundary identification during subsequent surgery. For patients receiving neoadjuvant therapy, preoperative endoscopic marking of the lesion enhances tumor localization and facilitates precise resection planning. Recommendation 3: Intraoperative endoscopic assessment is strongly recommended to achieve accurate tumor localization during laparoscopic procedures. Effective techniques include submucosal injection of contrast agents, preoperative titanium clip placement for marking, and intraoperative endoscopic verification. (Quality of evidence: B; strength of recommendation: strong; level of consensus: 100% agreement). Utilization of endoscopy for the evaluation of anastomoses in laparoscopic gastric tumor surgeries Intraoperative digestive endoscopy facilitates real-time evaluation of anastomoses during laparoscopic gastric tumor surgeries, providing critical visualization of potential complications, including anastomotic leakage, hemorrhage, stenosis, torsion, and impaired vascular perfusion. This approach enables timely intraoperative corrective measures, significantly reducing the likelihood of postoperative complications. Evidence from several randomized controlled trials (RCTs) has demonstrated that the use of intraoperative endoscopy is associated with a reduced incidence of anastomotic leakage.[15–16] Recommendation 4: The incorporation of intraoperative endoscopy in laparoscopic gastric surgery is strongly recommended for the assessment and management of potential anastomotic complications, including leakage, hemorrhage, and stenosis, to enhance overall surgical safety. (Quality of evidence: B; strength of recommendation: strong; level of consensus: 92% agreement, 4% disagreement, 4% abstention). Technical Features of Various LECS Procedures (1) Conventional LECS: The conventional LECS technique was first introduced by Naoki Hiki et al[17] in 2008. This procedure entails the endoscopic localization of the gastric lesion, followed by laparoscopy-assisted full-thickness resection of the gastric wall. The defect in the gastric wall is subsequently repaired using laparoscopic suturing or closure techniques. (2) Reverse LECS: This procedure, first reported by Souya Nunobe et al[18] in 2012, represents an adaptation of the classical approach. In this method, the submucosal layer surrounding the tumor is first dissected endoscopically. Sutures are then used to lift the gastric wall around the lesion, facilitating tumor inversion into the gastric cavity via traction. The full-thickness gastric wall incision is subsequently closed using a stapler, and the tumor specimen is extracted orally under endoscopic guidance. (3) Combined laparoscopic and endoscopic approach for neoplasia with nonexposure technique (CLEAN-NET): CLEAN-NET was first described by Inoue et al[19] in 2012. This method begins with marking both the mucosal and serosal surfaces. Full-layer suturing of the predefined serosal incision line is performed in four directions to elevate and stabilize the lesion. The seromuscular layer is subsequently excised outside the suture line, and the lesion is lifted via sutures traversing the entire gastric wall. The mucosal layer is then resected and closed laparoscopically with a cutter/stapler, while the seromuscular layer is sutured. The tumor specimen is extracted laparoscopically, ensuring continuity of the mucosal layer throughout the procedure. (4) Nonexposed endoscopic wall-inversion surgery (NEWS): NEWS was introduced by Osamu Goto et al[20] in 2011. This procedure involves marking the lesion on both the mucosal and serosal surfaces, followed by the creation of a submucosal fluid cushion through the injection of fluid beneath the mucosa. The seromuscular layer is then divided laparoscopically, and a spacer is inserted before the serosal surface is sutured. The lesion is inverted into the gastric cavity for endoscopic submucosal resection. Tumor specimens are extracted orally under endoscopic guidance. (5) Closed-LECS: In 2017, Nishizaki et al[21] introduced the closed-LECS procedure, which begins with the endoscopic marking of the mucosal layer and circumferential incision of the designated area. The serosal layer is marked according to the submucosal resection line. A sponge spacer is placed on the serosal surface, and the seromuscular layer is sutured to invert both the lesion and the spacer into the gastric cavity. The seromuscular layer is then dissected circumferentially under endoscopic visualization, and the specimen, along with the spacer, is extracted orally. Utilization of LECS in the Surgical Management of Gastric SMTs Gastric SMTs, predominantly comprising gastrointestinal stromal tumors or leiomyomas, present varying therapeutic challenges on the basis of their size and anatomical location. SMTs with a diameter of ≤2 cm are amenable to endoscopic excision, whereas those exceeding 2 cm generally necessitate surgical resection.[22–23] Traditional laparoscopic wedge resection is often complicated by the anatomical positioning of SMTs, particularly endophytic tumors located in the posterior corpus wall, gastroesophageal junction, or pylorus. The integration of LECS offers a robust solution, enabling the resection of gastric SMTs in anatomically challenging regions. This hybrid approach mitigates surgical complexity, enhances tumor exposure, facilitates precise excision while maintaining oncological principles, and preserves gastric anatomy and function, thereby optimizing postoperative outcomes and improving quality of life.[24] The classical exposed LECS technique has broad applicability for SMTs across diverse gastric locations. However, this method is associated with an increased risk of tumor cell dissemination, restricting its use to SMTs without mucosal defects. In contrast, NEWS permits precise delineation of the resection area but is limited by its inability to extract larger lesions orally. Consequently, NEWS is more suitable for intrinsic SMTs ≤3 cm in diameter. For SMTs with a diameter ranging from 3–5 cm, CLEAN-NET is preferable.[25–26] This method ensures radical tumor resection while prioritizing surgical ease, with procedural selection guided by the tumor’s location and growth pattern.[27] Current evidence supporting the application of LECS in the treatment of gastric SMTs is derived from limited-scale studies, underscoring the necessity for further large-scale clinical trials to confirm its effectiveness and safety. A Japanese study involving 215 cases of LECS for gastric SMT resection reported a completion rate of 99.1%. Postoperative complications of Clavien–Dindo classification grade II or higher occurred in six patients (2.8%), with delayed gastric emptying being the most common. The 3-year overall survival (OS) rate was reported to be 99%.[28] Similarly, a study conducted at Nanfang Hospital in China demonstrated a significant reduction in intraoperative complications with LECS compared with endoscopic resection.[29] Recommendation 5: LECS represents a viable approach for the surgical management of gastric SMTs located in challenging regions, such as the proximal gastroesophageal junction or pylorus, where endoscopic resection is often inadequate. This technique preserves digestive tract function and allows for tailored procedural selection on the basis of the tumor’s anatomical location and growth characteristics. (Quality of evidence: B; strength of recommendation: strong; level of consensus: 92% agreement, 8% abstention). Utilization of LECS in the Treatment of EGC EGC is characterized by tumors limited to the gastric mucosa or submucosa, irrespective of the extent of the lesion or the presence of lymph node metastasis.[30] The prevalence of EGC in China is increasing annually as a result of the widespread adoption of endoscopic screening methods. A considerable proportion of EGC cases are associated with lymph node metastasis, with reported rates of 2.2% to 6.9% in patients with cT1a tumors and 17.9% to 21.3% in those with cT1b tumors.[31–35] Given the critical role of tumor staging in determining appropriate therapeutic strategies, a thorough preoperative evaluation is essential. This should encompass advanced diagnostic modalities such as magnifying endoscopy, endoscopic ultrasound, and contrast-enhanced computed tomography (CECT), which facilitate precise assessment of tumor invasion depth and risk of lymph node metastasis.[34] Recommendation 6: A comprehensive preoperative evaluation employing magnifying endoscopy, endoscopic ultrasound, and CECT is recommended to ensure accurate tumor staging and to guide the selection of the most appropriate surgical approach. (Quality of evidence: B; strength of recommendation: strong; level of consensus: 96% agreement, 2% disagreement, 2% abstention). Endoscopic submucosal dissection (ESD) is the preferred therapeutic approach for most patients with T1a gastric cancer, with the following primary indications: (1) differentiated intramucosal carcinoma (cT1a) without ulceration; (2) differentiated intramucosal carcinoma (cT1a) with ulceration and a tumor ≤3 cm in maximum diameter; and (3) undifferentiated intramucosal carcinoma (cT1a) without ulceration and a tumor ≤2 cm in maximum diameter. A statistical analysis involving 5265 patients with EGC revealed the following significant risk factors for lymphatic metastasis: tumor diameter >3 cm, undifferentiated histology, presence of ulceration, vascular invasion, and depth of tumor invasion.[35] Lesions exhibiting poor tissue differentiation, ulcers, or scarring are associated with an elevated risk of extramucosal invasion and carry a greater likelihood of bleeding and perforation during endoscopic procedures. The endoscopic curability (eCura) system provides a valuable framework for evaluating survival outcomes and the risk of lymphatic metastasis in patients with EGC following endoscopic surgery. Notably, noncurative resections classified as eCuraC demonstrate an increased risk of residual cancer and lymphatic metastasis. In one study investigating partial gastrectomy combined with sentinel lymph node dissection for EGC with eCura C-2 (eCuraC-2), a lymphatic metastasis rate of 9.1% was reported.[36] The optimal salvage surgical strategies for these patients remain contentious. A Korean study compared the 10-year outcomes of endoscopic full-thickness gastric resection (EFTGR) with laparoscopic lymph node dissection (LLND) vs. ESD plus LLND in patients with EGC exceeding the absolute indications for ESD. The findings revealed identical local recurrence and mortality rates of 3.6% in the EFTGR plus LLND cohort. The study concluded that endoscopic resection followed by LLND does not increase the 10-year mortality rate in patients with EGC exceeding absolute ESD indications, thereby validating the safety and efficacy of LECS.[37] For patients with gastric cancer at high risk for ESD—such as those with EGC characterized by undifferentiated ulcerative T1a lesions >2 cm or T1b lesions ≤3 cm—and for patients prone to complications such as bleeding, perforation, or stenosis following endoscopy, a combined endoscopic and laparoscopic approach may be considered. This technique enables precise tumor resection and appropriate lymph node dissection, achieving radical tumor clearance while preserving postoperative quality of life by minimizing the extent of lymph node dissection and gastric wall resection. As a novel modality within the domain of minimally invasive surgery, this approach underscores the dual objectives of radical cure and functional preservation.[38] LECS has the potential to expand the indications for endoscopic resection of EGC, optimize gastric function preservation, enhance postoperative quality of life, and improve overall clinical outcomes. This technique addresses certain limitations associated with conventional laparoscopic or endoscopic surgeries when performed in isolation. However, the current evidence supporting LECS primarily originates from small-sample, single-center studies, and there is a notable lack of robust data from high-quality clinical trials to substantiate its safety and effectiveness. Consequently, the application of LECS in clinical practice should be approached with caution. For elderly or frail patients with a strong preference for functional preservation, LECS may be considered following comprehensive patient counseling and shared decision-making. Recommendation 7: LECS is indicated for precise local resection of EGC lesions that exceed the criteria for standard endoscopic treatment, particularly in patients with an elevated risk of lymph node involvement or complications such as bleeding, perforation, and stenosis following endoscopic treatment. This approach also enables targeted lymph node dissection, ensuring radical tumor resection with functional preservation. However, given the limited availability of high-quality clinical evidence, the clinical implementation of LECS should proceed cautiously and be restricted to experienced centers. (Quality of evidence: C; strength of recommendation: weak; level of consensus: 83% agreement, 17% abstention). Selecting the appropriate LECS procedure is also important. The classical exposed LECS technique carries a potential risk of tumor cell dissemination; therefore, nonexposed LECS techniques (e.g., NEWS, closed-LECS, or CLEAN-NET) combined with laparoscopic regional lymph node dissection are recommended. Preliminary studies, albeit with limited sample sizes, have demonstrated the feasibility, safety, and effectiveness of CLEAN-NET and NEWS in conjunction with LLND for patients with T1a or T1b EGC.[39–41] Nevertheless, there remains an unmet need for multicenter prospective clinical trials and comprehensive long-term outcome data to substantiate these findings. The pathways through which gastric cancer metastasizes to the lymph nodes are highly complex, with approximately 13% of patients exhibiting skip metastasis. Notably, only 62% of sentinel lymph nodes harboring metastasis are located adjacent to the primary for gastric cancer facilitates the identification of lymph nodes through preoperative or intraoperative injection of such as or carbon thereby enabling more precise intraoperative regional lymph node However, significant in the precision and of both and intraoperative lymphatic are there is a of evidence to guide clinical practice. The optimal extent of lymph node dissection remains and procedural is Recommendation For patients with EGC, nonexposed LECS is to the risk of tumor The use of and is to facilitate regional lymph node However, the precise extent of lymphatic dissection remains and further (Quality of evidence: C; strength of recommendation: weak; level of consensus: agreement, 4% disagreement, 17% abstention). 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