World J Transl Med. Nov 28, 2026; 12(4): 123849 Published online Nov 28, 2026. doi: 10.5528/wjtm.123849
Heterogeneity-oriented multidisciplinary and super-minimally invasive precision treatment framework for locally advanced gastric cancer
Qian-Qian Chen, Jia-Yan Zhou, En-Qiang Linghu
Qian-Qian Chen, Jia-Yan Zhou, En-Qiang Linghu, Department of Gastroenterology, The First Medical Center, General Hospital of the Chinese PLA, Beijing 100853, China
Co-first authors: Chen QQ and Zhou JY.
Author contributions: Chen QQ and Zhou JY contributed equally to this work as co-first authors; Linghu EQ supervised the study; all authors reviewed and approved the final manuscript.
AI contribution statement: We used DeepSeek to revise the language of the article in English.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: En-Qiang Linghu, MD, PhD, Chief Physician, Professor, Department of Gastroenterology, The First Medical Center, General Hospital of the Chinese PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. linghuenqiang@vip.sina.com
Received: June 1, 2026 Revised: July 18, 2026 Accepted: September 4, 2026 Published online: November 28, 2026 Processing time: 158 Days and 18.3 Hours
Abstract
Locally advanced gastric cancer, defined here as cT3-T4a disease with or without regional lymph node involvement and without distant metastasis, is characterized by substantial spatial and clonal heterogeneity. Distinct hypoxic, proliferative, invasive, immune-evasive, and treatment-resistant subpopulations may coexist within the primary tumor, the serosal-peritoneal interface, and regional lymph nodes. Standard perioperative systemic therapy and gastrectomy with D2 lymphadenectomy remain the established curative-intent treatment for resectable locally advanced gastric cancer; however, a uniform stage-based strategy may not fully represent the biological complexity of these tumors. To this end, we refined the Heterogeneity-oriented multidisciplinary team planning and super minimally invasive precision resection concept as a hypothesis-driven treatment framework rather than a clinically validated alternative to standard surgery. The framework comprises preoperative probabilistic heterogeneity mapping, heterogeneity-focused multidisciplinary decision-making, anatomically appropriate local treatment using endoscopic, laparoscopic or combined approaches, explicit management of the serosal-peritoneal and regional lymph node compartments, and postoperative biomarker-informed and risk-informed therapy. The proposed functional zones are not fixed anatomical layers, and endoscopic super minimally invasive surgery alone is insufficient for cT3-T4a disease. In particular, cT4a serosal involvement belongs to a serosal-peritoneal interface zone that requires laparoscopic evaluation and oncological control, while regional nodal disease requires guideline-concordant lymph node management. The model currently lacks primary clinical data, and claims of lower morbidity or superior long-term outcomes are not supported. Future validation should entail radiologic and pathologic mapping studies, followed by prospective feasibility studies measuring technical success, R0 resection, serosal and nodal control, perioperative complications, functional preservation, recurrence and survival. Heterogeneity-oriented multidisciplinary team planning and super minimally invasive precision resection should therefore be viewed as a testable framework for selected patients and clinical trials, with oncological adequacy taking priority over organ preservation.
Core Tip: Heterogeneity-oriented multidisciplinary team planning and super minimally invasive precision resection is an investigational heterogeneity-oriented framework, not a substitute for standard D2 gastrectomy. The central requirement of this concept is that any function-preserving local intervention must also achieve adequate control of the full gastric wall, the serosal-peritoneal interface, and regional lymph nodes. Endoscopy alone cannot meet these requirements in cT3-T4a disease; therefore, implementation would require a carefully selected, combined endoscopic-laparoscopic pathway and prospective validation.
