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Overview and Recommendations
Background
- •Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer death. Surgical resection with curative intent is the mainstay for localized disease, with the goal of R0 resection and adequate lymphadenectomy. The management is stage-dependent: early gastric cancer (T1) may be amenable to endoscopic resection or limited surgery, while locally advanced disease (T2-4 or N+) requires D2 gastrectomy with perioperative chemotherapy.
- •The paradigm has shifted from surgery alone to multimodality therapy. In the West, perioperative chemotherapy (MAGIC trial: ECF; FLOT regimen) improved overall survival (HR 0.75). In Asia, adjuvant S-1 (ACTS-GC) and neoadjuvant DOS followed by S-1 (PRODIGY) have become standards. The four pillars of modern management are adequate surgery, perioperative systemic therapy, lymphadenectomy, and ERAS.
- •Key surgical approaches include distal gastrectomy, total gastrectomy, and proximal gastrectomy. Lymphadenectomy extent (D1 vs D2) impacts outcomes: D2 dissection improves disease-specific survival compared with D1 (HR 0.807; NNT = 10). At least 16 lymph nodes should be assessed for adequate staging.
- •Laparoscopic gastrectomy has been validated in multiple randomized controlled trials (KLASS-01, KLASS-02, LOGICA, CLASS-02) as oncologically noninferior to open surgery, with equivalent 5-year overall survival and fewer early and late complications. Robotic gastrectomy offers technical advantages in lymph node dissection, particularly in narrow spaces.
- •Function-preserving techniques are emerging for early gastric cancer. Pylorus-preserving gastrectomy (PPG) for middle-third cT1N0 tumors reduces bile reflux, gallstone formation, and nutritional deficiencies. Sentinel node navigation surgery (LSNNS) allows stomach preservation in 74.8% of patients with cT1N0 tumors ≤3 cm, with 3-year disease-specific survival of 99.1%.
- •Enhanced recovery after surgery (ERAS) protocols have become standard of care. ERAS shortens hospital stay by ~1.8 days, reduces overall complications (OR 0.63), and improves 3-year overall survival in stage III gastric cancer (; HR 0.57). Core elements include prehabilitation, opioid-sparing analgesia, early oral feeding, and selective omission of abdominal drains.
Evaluation
- •Suspect gastric cancer in patients with dyspepsia, weight loss, early satiety, iron deficiency anemia, or hematemesis. Upper endoscopy with biopsy is the diagnostic gold standard; obtain multiple biopsies from the tumor and surrounding mucosa.
- •Stage with contrast-enhanced CT of chest, abdomen, and pelvis to assess T stage, nodal involvement, and distant metastases. Endoscopic ultrasound (EUS) is essential for accurate T and N staging, especially for early tumors where endoscopic resection or limited surgery may be considered.
- •Assess HER2, MSI, and PD-L1 status on biopsy specimens to guide perioperative and systemic therapy decisions. HER2-positive tumors benefit from trastuzumab; MSI-high tumors are highly responsive to immune checkpoint inhibitors.
- •For early gastric cancer (cT1N0), evaluate eligibility for endoscopic resection (differentiated type, ≤2 cm, no ulceration) or sentinel node navigation (tumor ≤3 cm). If not eligible, proceed to laparoscopic gastrectomy with D1+ lymphadenectomy.
- •For locally advanced disease (cT2-4 or N+), multidisciplinary discussion is essential. Consider neoadjuvant chemotherapy: FLOT (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², 5-FU 2600 mg/m² as 24h infusion) every 2 weeks for 4 cycles in the West; DOS (docetaxel 50 mg/m², oxaliplatin 100 mg/m², S-1 80-120 mg/day) in Asia.
- •Assess patient fitness for surgery: performance status (ECOG 0-2), nutritional status (NRS-2002), and frailty (Geriatric 8 score). Use preoperative risk stratification tools such as the Comprehensive Inflammatory-Metabolic Index (CIMI) to predict complications (AUC 0.748).
- •Preoperative imaging should include assessment of left gastric vein (LGV) anatomy on CT. Type C LGV (dorsal to splenic artery) predicts a 17.9% risk of postoperative pancreatic fistula (POPF) vs 1.7% for other types.
- •Consider staging laparoscopy for patients at high risk of peritoneal metastases: signet ring histology, diffuse type, advanced T stage (T3/T4), or suspicious findings on CT. Laparoscopy can detect occult peritoneal disease and avoid unnecessary laparotomy.
- •For metastatic disease (stage IV), surgery is reserved for palliation of obstruction or bleeding. Systemic therapy is primary; trastuzumab plus chemotherapy for HER2-positive, nivolumab plus chemotherapy for PD-L1 CPS ≥5, and apatinib for third-line therapy.
- •Also consider fertility preservation in young patients with early gastric cancer. Pylorus-preserving gastrectomy or sentinel node navigation may be appropriate to maintain reproductive potential and long-term quality of life.
Management
- •For early gastric cancer (cT1N0, ≤3 cm): offer laparoscopic sentinel node navigation surgery (LSNNS) if available; stomach preservation achieved in 74.8% of patients. If not eligible, perform laparoscopic distal gastrectomy with D1+ lymphadenectomy. For middle-third tumors, consider pylorus-preserving gastrectomy (PPG) to reduce bile reflux and nutritional deficiencies.
- •For locally advanced gastric cancer (cT2-4 or N+): administer perioperative chemotherapy. In the West, use FLOT (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², 5-FU 2600 mg/m² as 24h infusion) every 2 weeks for 4 cycles before and 4 cycles after surgery. In Asia, neoadjuvant DOS (docetaxel 50 mg/m², oxaliplatin 100 mg/m², S-1 80-120 mg/day) followed by D2 gastrectomy and adjuvant S-1 for 1 year.
- •Perform D2 lymphadenectomy (removal of perigastric nodes plus nodes along celiac axis, splenic artery, common hepatic artery, and left gastric artery). Aim for at least 16 lymph nodes. Use indocyanine green (ICG) fluorescence to improve nodal yield, especially after neoadjuvant therapy (mean difference 9.3 nodes) and in obese patients (mean difference 10.94 nodes).
- •For patients who undergo upfront surgery without neoadjuvant therapy and have T3+ or node-positive disease: administer adjuvant chemoradiation (45 Gy with 5-FU/leucovorin) per INT-0116. However, after D2 dissection, adjuvant chemotherapy alone (S-1 or SOX) is preferred based on CRITICS and ARTIST 2 data.
- •For stage III node-positive disease after D2: use S-1 (80-120 mg/day, 4 weeks on/2 weeks off for 1 year) plus docetaxel (JACCRO GC-07) to improve 3-year relapse-free survival from 50% to 66% (NNT=6). Alternatively, SOX (S-1 80-120 mg/day days 1-14, oxaliplatin 130 mg/m² day 1, every 3 weeks for 6 months) is effective (ARTIST 2).
- •For HER2-positive advanced disease: add trastuzumab (8 mg/kg loading, then 6 mg/kg every 3 weeks) to chemotherapy (capecitabine/cisplatin or 5-FU/oxaliplatin). After trastuzumab failure, anbenitamab plus chemotherapy improves PFS (HR 0.25) and OS (HR 0.29).
- •For MSI-high advanced disease: use pembrolizumab or nivolumab plus chemotherapy. Anti-PD-1 regimens yield OS HR 0.34 in MSI-high vs 0.85 in MSS (P interaction = 0.003).
- •Intraoperative management: use a pancreas-contactless technique to reduce POPF (from 7.6% to 0% in open gastrectomy). Perform intraoperative air-leak test for anastomotic integrity. Have a low threshold for conversion to open if bleeding is not rapidly controlled laparoscopically.
- •Postoperative ERAS: initiate early oral feeding (clear liquids on POD 1, soft diet by POD 3-4), multimodal opioid-sparing analgesia (subcostal TAP block, acetaminophen, COX-2 inhibitors), early mobilization, and selective omission of abdominal drains. Discharge criteria: tolerating oral intake, pain controlled with oral analgesics, afebrile, ambulating independently.
- •Monitor for complications: pancreatic fistula (POPF) - manage with drainage, nil per os, parenteral nutrition, somatostatin analogues; anastomotic leak - endoscopic stenting or percutaneous drainage; reoperation for large defects. Use preoperative LGV anatomy to stratify POPF risk.
- •Avoid: non-dihydropyridine CCBs (diltiazem, verapamil) - exacerbate gastroparesis; routine abdominal drainage - increases complications (OR 0.53 for omission); routine radiotherapy after D2 dissection - no benefit (ARTIST 2); ELFE, FAMTX, or FEMTX regimens - no survival benefit; adjuvant nivolumab/ipilimumab for ypN+/R1 after neoadjuvant chemo - inferior to chemotherapy (VESTIGE).
- •Refer to medical oncology for perioperative therapy and management of advanced disease. Refer to radiation oncology if adjuvant chemoradiation is indicated (inadequate lymphadenectomy or R1 resection). Refer to palliative care for symptom management in advanced disease.
- •For young patients with early gastric cancer: consider pylorus-preserving gastrectomy or sentinel node navigation to preserve fertility and long-term quality of life. Discuss fertility preservation options preoperatively.
- •Long-term surveillance: clinical follow-up with history, physical exam, and contrast-enhanced CT every 3-6 months for first 2 years, then every 6-12 months. Endoscopy as indicated for symptoms. Monitor nutritional status with NRS-2002 every 2 weeks for first 3 months; oral nutritional supplements if needed, target 25-30 kcal/kg/day and protein 1.0-1.5 g/kg/day.
Board Review — High Yield
- •MAGIC trial, Perioperative ECF chemotherapy improved overall survival (HR 0.75) compared to surgery alone for resectable gastric cancer.
- •D2 lymphadenectomy, Improves disease-specific survival over D1 (HR 0.807); at least 16 lymph nodes required for adequate staging.
- •KLASS-01, Laparoscopic distal gastrectomy noninferior to open for stage I gastric cancer (5-year OS 94.2% vs 93.3%).
- •S-1 plus docetaxel (JACCRO GC-07), For stage III after D2, improves 3-year RFS from 50% to 66% (NNT=6).
- •ERAS (GISSG1901), Reduces complications, hospital stay, and improves 3-year survival in stage III gastric cancer (HR 0.57).
- •Sentinel node navigation (SENORITA), For cT1N0 tumors ≤3 cm, detection rate 97.5%, accuracy 99%; stomach preservation in 74.8%.
- •Pylorus-preserving gastrectomy (KLASS-04), For middle-third early gastric cancer, reduces bile reflux, gallstone formation, and nutritional deficiencies.
- •ICG fluorescence, Increases lymph node yield by 6.9 nodes (mean), especially after neoadjuvant therapy and in obese patients.
- •CRITICS trial, After D2, adjuvant chemotherapy alone superior to chemoradiation (5-year OS 57.9% vs 45.5%; adjusted HR 1.62).
- •VESTIGE trial, Nivolumab/ipilimumab inferior to chemotherapy for ypN+/R1 after neoadjuvant chemo (median DFS 11.4 vs 20.8 months; HR 1.55).
Deep Dive — Evidence Details
Indications by Stage
- ▸D2 gastrectomy + perioperative chemotherapy is standard for locally advanced disease.
- ▸LSNNS is a stomach-preserving option for select early gastric cancer.
Surgical management of is stage-dependent. For early gastric cancer (cT1N0, ≤3 cm), laparoscopic sentinel node navigation surgery (LSNNS) allows stomach preservation in 81% of patients, with 3-year disease-specific survival of 99.1% vs. 99.5% for standard [18]A1b. For locally advanced (T2-4, N+), D2 gastrectomy with perioperative chemotherapy is standard. The MAGIC trial established perioperative ECF ( , , fluorouracil) improving OS (HR 0.75) [7]A1b. PRODIGY showed neoadjuvant DOS ( , , S-1) followed by D2 surgery and adjuvant S-1 improved PFS (HR 0.70) [10]A1b[13]A1b. After upfront surgery, adjuvant chemoradiation (INT-0116) reduces relapse (HR 1.51) [14]A1b. For metastatic disease, surgery is palliative only. Pearl: For locally advanced gastric cancer, D2 gastrectomy with perioperative chemotherapy (MAGIC-style ECF/X or PRODIGY-style DOS) is the evidence-based standard; adjuvant chemoradiation is an alternative for patients who did not receive neoadjuvant therapy, but after D2 dissection, adjuvant chemotherapy alone may be preferred based on CRITICS data.
Operative Techniques
- ▸Minimally invasive gastrectomy has randomized-trial evidence addressing **5-year OS and DFS**, but the supplied meta-analysis abstract does not provide pooled estimates [29].
- ▸Robotic gastrectomy may reduce blood loss and severe complications but generally requires longer operating time and greater resources [131,133,143].
- ▸ICG fluorescence can support lymphatic mapping, hepatic-perfusion assessment during ALHA management, and structured robotic-program implementation [72,130].
- ▸CVQ and CT-based radiomics are emerging tools for assessing or predicting lymphadenectomy quality and difficulty, but neither replaces pathological assessment [141,144].
- ▸PPG and CLEAN-NET should be restricted to carefully selected early-stage disease because evidence for broader oncologic application remains limited [137,140].
- ▸Prehabilitation and perioperative prediction tools may improve risk stratification and adjuvant-treatment delivery, but most supporting evidence is observational or requires validation [25,132,139].
Surgical approach and oncologic principles
Gastrectomy should be selected according to tumor location, clinical stage, resectability, patient fitness, institutional expertise, and the requirement for an oncologically appropriate lymphadenectomy. Minimally invasive gastrectomy (MIG), encompassing laparoscopic and robotic approaches, is an established alternative to open gastrectomy for appropriately selected resectable disease; randomized-trial meta-analytic evidence evaluating 5-year overall survival (OS), stage-specific OS, and 5-year disease-free survival (DFS) addresses long-term oncologic safety, although the supplied abstract does not provide the pooled estimates [29]A1a. In advanced gastric cancer, laparoscopic gastrectomy has been evaluated across Japanese and Italian centers using severe morbidity, mortality, R0 resection, and lymph-node yield as principal quality outcomes, emphasizing that safe adoption depends on standardized technique and institutional experience [135].
For post-chemotherapy cStage IVb disease undergoing curative-intent resection, minimally invasive surgery (MIS) has been compared with open surgery in a multicenter retrospective cohort with propensity-score matching; this evidence supports MIS as a selectively assessable option rather than a universal substitute for systemic therapy or open surgery [52]B3b. Conversion surgery remains a treatment strategy for initially unresectable stage IV gastric or gastroesophageal-junction cancer that becomes resectable after systemic therapy, and the role of first-line nivolumab-based treatment in selecting such patients has been examined in propensity-matched real-world data [136].
Laparoscopic and robotic gastrectomy
Robotic gastrectomy can be used for radical gastrectomy and lymphadenectomy, but available comparative evidence indicates a trade-off between technical capability and resource use. A meta-analysis of 17 studies involving 31,573 patients reported longer operative time with robotic versus open gastrectomy, with a weighted mean difference of 93.4 minutes, while blood loss was lower by a weighted mean difference of 86.71 mL; the supplied abstract does not report all postoperative and oncologic endpoints [133]. A propensity-score-matched study of advanced gastric cancer compared 154 robotic and 154 laparoscopic cases and assessed severe morbidity, postoperative inflammation, delivery of adjuvant chemotherapy, recurrence patterns, OS, and relapse-free survival; the abstract reports that robotic surgery independently reduced severe complications, but does not provide the effect estimate or complete survival results [131].
In patients aged ≥75 years, a retrospective comparison of robotic and laparoscopic gastrectomy included 316 elderly patients—233 laparoscopic and 83 robotic—and reported longer operative time with robotic surgery in both elderly and non-elderly cohorts; the abstract does not provide the complete complication and survival estimates [143]. Robotic surgery may therefore be considered when enhanced instrument articulation, visualization, or dissection ergonomics are valuable, but its use should be balanced against longer operating time and higher cost reported in the comparative literature [131][133][143].
A randomized trial in robot-assisted distal gastrectomy compared a laparoscopic-like 3-arm + 2-port configuration with the traditional 4-arm + 1-port configuration during Billroth II reconstruction with Braun anastomosis and D2 lymphadenectomy. The trial evaluated operative time, blood loss, lymph-node yield, and postoperative outcomes, but the supplied abstract does not report the comparative results [33]A1b. Port configuration should consequently be individualized to the robotic platform, surgeon ergonomics, target anatomy, and the planned reconstruction [33]A1b.
Lymphatic mapping and dissection quality
Indocyanine-green (ICG) near-infrared lymphography may assist tumor localization and lymph-node dissection during robotic gastrectomy. A structured implementation study introduced robotic gastrectomy stepwise, beginning with subtotal and progressing to total gastrectomy after formal training, and evaluated perioperative outcomes and the diagnostic accuracy of ICG-guided lymphography; this low-level evidence supports protocolized training and staged case selection during program development [72]C4.
The quality of minimally invasive lymphadenectomy can be assessed intraoperatively using the anatomy-based Critical View of Quality (CVQ), which evaluates completeness across five nodal stations. In a retrospective series of 260 laparoscopic or robotic distal gastrectomies, CVQ was correlated with lymph-node yield and used to develop a computer-vision model for automated video assessment; CVQ is therefore a potential quality-assurance adjunct, but it is not established as a substitute for pathology or long-term oncologic endpoints [144]. Preoperative CT-based radiomics of suprapancreatic adipose tissue has also been investigated to predict high-difficulty lymph-node dissection, defined as suprapancreatic dissection time exceeding the 75th percentile, with a training cohort of 134 and validation cohort of 58 patients; this may support operative planning but remains retrospective and single-center evidence [141].
When an aberrant left hepatic artery (ALHA) is encountered, preservation or ligation should account for oncologic requirements and hepatic perfusion. A prospective, non-randomized multicenter study of 50 minimally invasive gastrectomy patients used temporary ALHA clamping followed by intravenous ICG and near-infrared fluorescence assessment of left-lobe perfusion, categorizing patients according to absent, partial, or preserved fluorescence; the reported algorithm is investigational and should not replace individualized vascular and oncologic judgment [130].
Function-preserving and limited resections
Pylorus-preserving gastrectomy (PPG) is a function-preserving option for selected early tumors, particularly when oncologically appropriate. In patients aged ≥75 years with cT1N0M0 disease, a retrospective comparison of laparoscopic PPG and laparoscopic distal gastrectomy with Billroth I reconstruction evaluated CT-based bone mineral density and vertebral fractures at 1, 3, and 5 years; PPG was associated with more favorable long-term bone-health outcomes in the reported cohort, although selection bias limits generalization [140]. CLEAN-NET, a non-exposure laparoscopic and endoscopic cooperative technique, has been evaluated in only 19 patients with clinically cT1N0 disease and selective limited nodal assessment; its long-term oncologic validity remains uncertain and it should not be generalized to node-positive or advanced disease [137]C.
Perioperative optimization and recovery
Operative planning should incorporate risk reduction and postoperative treatment continuity. Multimodal prehabilitation involving medical, physical, nutritional, and psychological optimization has been studied in esophagogastric cancer surgery, with pulmonary complications and resilience to major postoperative events as outcomes [139]. A multimodal deep-learning model was developed in 5,237 patients to predict postoperative complications and long-term survival, while the NUTRISCORE nomogram was developed in 391 patients receiving postoperative CAPEOX/XELOX/SOX after curative laparoscopic D2 gastrectomy to predict grade 3/4 neutropenia across cycles 2–8; these tools may support selection and adjuvant-treatment planning but require external validation before routine use [25]C4[132]. For proximal gastric or gastroesophageal operations involving minimally invasive esophagectomy, early postoperative CT has been studied for suspected anastomotic leakage, but this evidence is not directly transferable to standard gastrectomy [138].
| Technique or adjunct | Evidence and reported findings | Practical implication |
|---|---|---|
| MIG versus open gastrectomy | Randomized-trial meta-analysis assessed 5-year OS, stage-specific OS, and 5-year DFS [29]A1a | Use MIG when oncologic resection is feasible and expertise is available |
| Robotic gastrectomy | Longer operative time than open surgery: 93.4 minutes; lower blood loss: 86.71 mL [133] | Balance potential technical benefits against time, cost, and training requirements |
| Robotic versus laparoscopic surgery | Propensity-matched advanced-cancer study reported independently fewer severe complications with robotic surgery; complete estimates unavailable in the supplied abstract [131] | Consider selectively; survival benefit is not established from the supplied data |
| ICG lymphography | Used for lymphatic mapping and ALHA perfusion assessment; ALHA study included 50 patients [72]C4[130] | Apply as an adjunct to anatomy-based dissection and vascular judgment |
| CVQ and radiomics | CVQ evaluates five nodal stations; radiomics predicted high-difficulty suprapancreatic dissection [141][144] | Support quality assurance and preoperative planning, pending validation |
| PPG/CLEAN-NET | PPG studied in elderly cT1N0M0 disease; CLEAN-NET included 19 cT1N0 patients [137]C[140] | Reserve for rigorously selected early cancers |
Fertility-Sparing Surgery
- ▸PPG preserves pyloric function and reduces nutritional deficiencies.
- ▸Indicated for cT1N0M0 middle-third tumors ≥4 cm from pylorus.
For young patients with early , function-preserving approaches minimize long-term morbidity. Pylorus-preserving (PPG) is indicated for cT1N0M0 middle-third tumors ≥4 cm from pylorus [32]A1b. By preserving the hepatic branch of the vagus nerve and infrapyloric vessels, PPG reduces gallstone formation, bile reflux, and postoperative nutritional deficiencies (KLASS-04 trial) [32]A1b. These benefits are critical for preserving fertility and pregnancy outcomes. PPG is technically demanding; advances in minimally invasive surgery and ICG imaging facilitate safe implementation [32]A1b. If postoperative pathology reveals advanced disease, standard adjuvant therapy is sufficient without additional resection [32]A1b. Pearl: For young patients with cT1N0M0 gastric cancer in the middle third, pylorus-preserving gastrectomy should be the preferred function-preserving approach, as it reduces postoperative nutritional deficiencies and bile reflux, supporting long-term quality of life and potentially fertility.
Sentinel Lymph Node Mapping
- ▸SNN is a selective, protocol-dependent strategy for EGC and should not routinely replace systematic lymphadenectomy [58,60].
- ▸Intraoperative sentinel-node pathology uses representative hematoxylin–eosin assessment, with permanent hematoxylin–eosin and cytokeratin immunohistochemistry evaluation [62].
- ▸SENORITA 2 is evaluating sentinel-basin mapping after non-curative ESD, a setting in which reported nodal-metastasis risk is approximately 5–10% [145].
- ▸For lymphadenectomy quality, **≥16 nodes** represents a proper dissection and **≥30 nodes** an ideal dissection [30].
- ▸ICG fluorescence can improve lymphatic visualization and may increase nodal retrieval, but fluorescence alone does not reliably prove metastatic-node status or nodal negativity [30,67].
- ▸Five-year FUGES-012 results showed superior overall and disease-free survival and lower recurrence with ICG-guided lymphadenectomy in the reported randomized cohort [57].
- ▸Evidence after neoadjuvant chemotherapy is supportive but heterogeneous and does not yet establish a universal ICG mapping protocol [66,146,148].
- ▸Carbon nanoparticles are a potential alternative tracer where near-infrared imaging equipment is unavailable, but comparative evidence remains limited [61,147].
Concept and current role
Sentinel lymph node mapping (SNN) identifies the first draining lymph nodes and their associated sentinel basins to permit tailored gastric resection and lymphadenectomy, particularly in carefully selected patients with early gastric cancer (EGC). The SENORITA phase III experience supports laparoscopic sentinel node navigation surgery (LSNNS) as a stomach-preserving strategy, although treatment failure and recurrence remain clinically relevant limitations [58]A1b. SNN should therefore be regarded as a selective approach rather than a replacement for oncologically indicated systematic lymphadenectomy; a post hoc SENORITA analysis explored regional lymphadenectomy without SNN because mapping can be technically difficult in routine practice [60]C4.
Mapping technique and intraoperative pathology
The SENORITA protocol used intraoperative evaluation of sentinel nodes to determine the extent of surgery. In the reported pathologic analysis, sentinel nodes were examined intraoperatively using hematoxylin–eosin staining of a representative section through the largest nodal plane; permanent assessment used hematoxylin–eosin staining and cytokeratin immunohistochemistry of sentinel-basin nodes [62]C4. This approach addresses the principal safety requirement of stomach-preserving surgery: a negative intraoperative sentinel-node assessment must reliably exclude clinically important nodal disease within the mapped basin [62]C4.
SENORITA data also indicate that the feasibility of stomach preservation is not uniform across all EGC presentations. A secondary analysis compared patients who successfully underwent stomach preservation without recurrence with those who experienced preservation failure or recurrence, emphasizing the need to identify clinicopathologic features associated with an unsafe or unsuccessful tailored approach [58]A1b. Regional lymphadenectomy without sentinel navigation has been investigated as a technically simpler alternative, with tumor location analyzed in longitudinal and circumferential dimensions and sentinel versus non-sentinel basin metastases assessed; this remains post hoc feasibility evidence rather than definitive validation of routine SNN omission [60]C4.
Sentinel mapping after non-curative endoscopic resection
Patients with non-curative endoscopic submucosal dissection (ESD) for EGC are conventionally considered for gastrectomy with systematic lymph-node dissection, although the reported incidence of lymph-node metastasis is approximately 5–10% [145]C. The prospective multicenter SENORITA 2 feasibility study evaluated sentinel-basin mapping in this setting using either dual-tracer endoscopic submucosal injection with a radioisotope and indocyanine green (ICG), or fluorescence imaging after ICG injection [145]C. This application may support risk-adapted surgery in selected patients, but the study was designed to establish feasibility, not to replace standard oncologic surgery for all patients with non-curative ESD [145]C.
ICG fluorescence lymphography as an adjunct to lymphadenectomy
ICG near-infrared fluorescence provides real-time visualization of lymphatic drainage and is increasingly used to guide minimally invasive gastrectomy. A 2026 systematic review and meta-analysis of randomized and non-randomized comparative studies evaluated ICG-guided versus standard minimally invasive lymphadenectomy, focusing primarily on retrieved-node count and secondarily on adequate lymphadenectomy, postoperative outcomes, recurrence, and mortality-related outcomes [30]A1a. The clinically relevant nodal thresholds are ≥16 retrieved nodes for a proper lymphadenectomy and ≥30 nodes for an ideal lymphadenectomy [30]A1a.
A separate systematic review and meta-analysis of NIR-ICG-guided versus conventional D2 dissection specifically examined whether results were reproducible across Eastern and Western cohorts [65]B2a. Reviews covering open, laparoscopic, and robotic procedures likewise evaluated node retrieval and perioperative outcomes, indicating that the potential benefit of ICG is relevant across minimally invasive platforms but that results may depend on operative setting, technique, and institutional experience [69]C4. Robotic-specific evidence also supports fluorescent lymphography as a real-time aid to lymphatic visualization and guided node dissection, although the robotic literature remains comparative and heterogeneous [68]B2a. A Western institutional implementation report described stepwise introduction of robotic gastrectomy with ICG-guided lymphography to support adequate lymphadenectomy and tumor localization during adoption of the technique [72]C4.
The strongest long-term comparative evidence comes from the FUGES-012 randomized clinical trial. In the per-protocol population of 258 patients—129 receiving ICG guidance and 129 standard surgery—the ICG group had superior 5-year overall and disease-free survival and a lower cumulative recurrence rate after 5 years, with recurrence reported in 26/129 patients (20.2%) in the ICG group [57]A1b. These findings suggest a possible oncologic advantage, but they should be interpreted in the context of the trial population and protocol rather than assumed to establish benefit in every stage or surgical environment [57]A1b.
Neoadjuvant chemotherapy and metastatic-node detection
The value of ICG after neoadjuvant chemotherapy (NAC) is particularly important because treatment-related fibrosis or altered lymphatic drainage could theoretically reduce mapping performance. A systematic review and meta-analysis including five studies and 694 patients compared ICG-guided with conventional lymphadenectomy after NAC, assessing retrieved-node count, the proportion achieving ≥30 nodes, non-compliance, blood loss, hospital stay, operative time, and complications [66]B2a. A separate retrospective cohort of patients with cT2–4N0/+M0 disease treated with NAC followed by laparoscopic radical gastrectomy evaluated the prognostic impact of ICG using overlap weighting [146]. A Western retrospective series of 34 patients further examined whether tumor response to NAC, classified by Mandard tumor-regression grade, influenced ICG-guided lymphadenectomy quality and perioperative outcomes [148]. These studies support investigation of ICG after NAC but do not establish a universal mapping protocol or prove that fluorescence independently improves survival in this setting [66]B2a[146][148].
Importantly, improved fluorescence visualization should not be equated with reliable identification of metastatic disease. A systematic review and meta-analysis of esophageal and gastric cancer resections found that the accuracy of ICG/NIR fluorescence for detecting metastatic nodes remains uncertain, despite its potential to increase total nodal yield and guide dissection [67]C4. A small randomized study evaluated combined ICG and endoscopic ultrasound (EUS) as an intraoperative navigation system for nodal assessment, but its sample size was only 26 patients, limiting generalizability [64]A1b.
Other fluorescence-guided applications relevant to mapping
Randomized evidence has compared ICG with carbon nanoparticle suspension for lymphatic mapping, intraoperative guidance, and postoperative node sorting in potentially resectable cT1–4aN0/+M0 gastric cancer; the FUTURE-01 trial enrolled 96 patients, with 90 included in the modified intention-to-treat population [61]A1b. Carbon nanoparticles may be an alternative where near-infrared equipment is unavailable, although comparative evidence remains limited; a propensity-matched study evaluated carbon nanoparticles, ICG, and control groups during laparoscopic distal gastrectomy [147].
Fluorescence imaging can also guide adjacent technical decisions rather than sentinel-node selection itself. In a prospective comparative study of 50 patients, ICG perfusion imaging after temporary clamping of an aberrant left hepatic artery was used to decide preservation or ligation according to left-lobe perfusion [130]. Randomized trials have additionally assessed ICG for proximal-margin identification during laparoscopic distal gastrectomy in 422 patients and for perigastric vagus-nerve preservation in early distal gastric cancer [56]A1b[59]A1b; these applications may improve operative navigation but should not be presented as validated sentinel-node techniques [56]A1b[59]A1b.
Practical interpretation
SNN is most defensible within validated protocols for selected EGC patients and requires meticulous tracer injection, basin identification, and intraoperative pathology [58]A1b[62]C4[145]C. ICG fluorescence lymphography is a useful adjunct for improving visualization and potentially increasing nodal retrieval, especially during minimally invasive D2 lymphadenectomy, but it does not by itself establish nodal negativity or replace adequate oncologic dissection [30]A1a[65]B2a[67]C4. The ≥16-node and ≥30-node benchmarks remain important quality thresholds when assessing the completeness of lymphadenectomy [30]A1a.
| Application | Evidence and interpretation |
|---|---|
| Sentinel-node navigation in EGC | SENORITA supports stomach-preserving surgery in selected patients, with recognized failure and recurrence risk [58]A1b. |
| Intraoperative sentinel-node pathology | Representative-section hematoxylin–eosin assessment is used intraoperatively; permanent assessment adds cytokeratin immunohistochemistry [62]C4. |
| Post-ESD sentinel-basin mapping | SENORITA 2 evaluates dual-tracer or ICG fluorescence mapping after non-curative ESD [145]C. |
| ICG-guided lymphadenectomy | Meta-analyses assess nodal yield, ≥16-node proper dissection, ≥30-node ideal dissection, and perioperative outcomes [30]A1a[65]B2a[69]C4. |
| ICG after NAC | Evidence addresses node yield, adequacy, complications, and possible prognostic effects, but remains heterogeneous [66]B2a[146][148]. |
| Metastatic-node detection | Diagnostic accuracy remains uncertain; ICG should not be treated as a stand-alone test for metastasis [67]C4. |
| Alternative tracers | Carbon nanoparticle suspension has been compared with ICG and may be useful where NIR equipment is unavailable [61]A1b[147]. |
Adjuvant Therapy Triggers
- ▸S-1 +/- docetaxel is standard for Asian D2-resected stage II/III.
- ▸Adjuvant radiotherapy is not indicated after D2 dissection.
Postoperative therapy is guided by pathology. For Asian patients with D2-resected stage II/III, S-1 monotherapy (80-120 mg/day, 4 weeks on/2 weeks off for 1 year) is standard (ACTS-GC, 5-year OS 71.7% vs. 61.1%) [77]A1b. For node-positive stage III, adding to S-1 improves 3-year RFS from 50% to 66% (HR 0.632; NNT=6) [12]A1b. SOX (S-1 plus 130 mg/m² q3 weeks) for 6 months is an alternative [73]A1b. For Western patients, perioperative FLOT or postoperative chemoradiation (45 Gy with FU/LV) is standard [14]A1b. After D2 surgery, chemotherapy alone is preferred (CRITICS: 5-year OS 57.9% vs. 45.5% with chemoradiation) [5]A1b. Do not use adjuvant nivolumab/ipilimumab in ypN+/R1 patients (VESTIGE: inferior DFS) [19]B2b. Pearl: For patients with D2-resected, node-positive stage III gastric cancer, the addition of docetaxel to S-1 yields a 3-year relapse-free survival benefit of 16 percentage points (NNT = 6) and should be considered the new standard in Asia, while routine radiotherapy after D2 dissection is not supported by current evidence.
Intraoperative Considerations and Complications
- ▸Use standardized complication definitions and severity grading after gastrectomy; the K-QIPS framework was developed through expert consensus across 14 high-volume hospitals. [149]
- ▸Assess pancreatic-injury risk during suprapancreatic dissection, including left gastric vein anatomy and pancreas-contactless exposure techniques. [93][94]
- ▸Consider frailty, sarcopenia, inflammatory-metabolic status, resting-energy-expenditure changes, nutritional status, and preoperative quality of life when estimating complication risk. [83][89][90][91][96]
- ▸Use multimodal or unimodal prehabilitation interventions lasting at least 7 days when feasible before gastric cancer resection. [151]
- ▸Individualize VTE prophylaxis; reported 90-day incidence after gastrointestinal cancer surgery was 2.1%, with risk associated with age, prior VTE, thrombophilia, hypoalbuminemia, and transfusion. [154]
- ▸Robotic, reduced-port, and novel port configurations may be feasible, but operative time, learning curve, patient selection, and available comparative evidence must be considered. [33][87][92][143]
Operative planning and technical execution
Gastrectomy should be planned according to tumor location, resectability, required lymphadenectomy, reconstruction, patient frailty, nutritional status, and anticipated technical difficulty. The available evidence includes distal, total, proximal, open, laparoscopic, and robotic procedures, but it does not establish one universally superior operative approach. A randomized controlled trial evaluated robot-assisted distal gastrectomy with Billroth II reconstruction, Braun anastomosis, and D2 lymphadenectomy using either a traditional 4-arm + 1-port or laparoscopic-like 3-arm + 2-port configuration; prespecified outcomes included operative time, blood loss, lymph-node yield, and postoperative recovery. [33]A1b
Robotic gastrectomy has been compared with laparoscopic gastrectomy in a systematic review and meta-analysis assessing perioperative outcomes and long-term overall, relapse-free, and disease-free survival. The review used ROB 2 and ROBINS-I V2, indicating that conclusions should account for both randomized and non-randomized evidence and possible study-quality limitations. [87]B2a In elderly patients, a retrospective study of 951 patients—including 316 patients aged ≥75 years—found that robotic gastrectomy was associated with longer operative time than laparoscopic gastrectomy in both elderly and non-elderly cohorts; the study specifically assessed safety and feasibility rather than providing evidence that robotics is universally preferable. [143]
Reduced-port robotics should be introduced after appropriate experience with the platform. In a propensity-score-matched analysis adjusted using cumulative-sum learning-curve methodology, 30 initial cases were excluded before comparing reduced-port and conventional robotic distal gastrectomy; the final analysis included 39 matched pairs and evaluated textbook outcomes, operative time, blood loss, lymph-node retrieval, and postoperative pain. [92]B3b The randomized 3-arm + 2-port study provides additional prospective evidence for laparoscopic-like port placement, although the supplied abstract does not report the comparative numerical results. [33]A1b
Prevention of procedure-specific injury
Suprapancreatic lymph-node dissection is a key site of potential pancreatic injury. A retrospective study of minimally invasive gastrectomy classified the preoperative left gastric vein route on contrast-enhanced CT into four patterns: type A, dorsal to the common hepatic artery; type B, ventral to the celiac artery; type C, dorsal to the splenic artery; and type D, within the lesser omentum. The study evaluated whether these patterns predicted clinically relevant postoperative pancreatic fistula using drain amylase levels or imaging findings. [93]C4 In open gastrectomy, a pancreas-contactless technique exposed the suprapancreatic region by retracting the root of the transverse mesocolon along the inferior pancreatic border rather than compressing the pancreas with gauze; this approach was compared retrospectively with pancreas-contact surgery for postoperative pancreatic complications. [94]B3b
Reconstruction is another source of technical morbidity. A preliminary series of 12 patients evaluated a trapezoidal-tunnel intracorporeal esophagogastric anastomosis after laparoscopic proximal gastrectomy. The technique uses extra-abdominal manipulation to create a tunnel in the remnant stomach and was designed to simplify intra-abdominal manipulation while addressing reflux concerns after esophagogastric reconstruction. [95]C4 Early postoperative CT assessment for suspected anastomotic leakage has also been studied in minimally invasive Ivor Lewis esophagectomy for esophageal or proximal gastric cancer; the retrospective cohort used independent reassessment by three radiologists and propensity-score matching, but diagnostic performance should not be extrapolated directly to standard gastrectomy without procedure-specific validation. [138]
Complication surveillance and classification
Postgastrectomy complications should be recorded using consistent definitions and severity grading. The Korean Quality Improvement Platform in Surgery task force developed a gastrectomy-specific complication classification through 10 formal meetings involving experts from 14 high-volume hospitals, reviewing literature, international guidelines, and randomized-trial findings. [149] Clinically important events include anastomotic leakage, pancreatic fistula, infection, bleeding, thromboembolism, and other medical or surgical complications; the cited consensus work was specifically intended to standardize their definition across institutions. [149]
In a prospective Romanian tertiary-center study, 211 adults undergoing elective gastric or colorectal cancer surgery were followed for 30 days to characterize healthcare-associated infections, their microbiology, antimicrobial resistance, and risk factors; the investigation assessed infections beyond surgical-site infection alone and evaluated neoadjuvant radiotherapy as a potential independent risk factor. [150]C A separate double-blind randomized trial enrolled patients undergoing open gastrectomy and administered probiotics or placebo for 10 days beginning on postoperative day 1, evaluating hospital stay, clinical outcomes, nutritional status, and inflammatory and immune markers. [153]
Risk stratification and prevention
Preoperative risk assessment should include inflammatory, metabolic, nutritional, functional, and patient-reported measures. A comprehensive inflammatory-metabolic index was developed from 567 stage II–III patients in four randomized controlled trials and externally validated in 107 patients; hematologic and body-composition variables were used to predict complications and prolonged hospitalization, with evaluation by ROC, precision-recall, decision-curve, and model-fit analyses. [83]A1b A dynamic machine-learning study of 193 elective gastrectomy patients assessed whether resting-energy-expenditure measurements obtained preoperatively and on postoperative day 1 improved prediction of Clavien–Dindo grade II or higher complications. [89]B2b
Prehabilitation is supported by a systematic review of randomized trials evaluating unimodal and multimodal interventions lasting at least 7 days before gastric cancer resection. The review examined whether optimization of physical and nutritional status improves perioperative resilience and characterized the reported outcomes across trials. [151] Frailty and sarcopenia are particularly relevant in older adults: a retrospective study of patients aged ≥70 years used comprehensive geriatric assessment and L3 skeletal-muscle index to examine associations with postoperative outcomes and survival. [91]C4 Preoperative quality of life may also aid risk prediction; among 908 gastrectomy patients, 189 (20.8%) developed postoperative complications, and EORTC QLQ-C30 and STO22 scores were evaluated in multivariable prediction models. [96]B3b The C-reactive-protein–albumin–lymphocyte index has been studied as an integrated inflammation, nutrition, and immunity marker, including its association with postoperative complications, in a systematic review and meta-analysis of gastrointestinal malignancies. [90]B2a
Thromboembolism and advanced disease
Venous thromboembolism prevention should be individualized using clinical risk factors and institutional protocols. In a real-world cohort of 2,702 patients undergoing gastrointestinal cancer surgery, the 90-day perioperative VTE incidence was 2.1%; higher risk was associated with older age, previous VTE, thrombophilia, low serum albumin, and blood transfusion, whereas procedure duration and surgical approach were not associated with VTE. [154]
For carefully selected gastric cancer with limited peritoneal metastasis, the prospective phase II ROBO-CHIP study evaluated laparoscopic HIPEC followed by robotic cytoreduction, gastrectomy, and HIPEC after at least 4 months of systemic chemotherapy in patients with PCI ≤7. The protocol used paclitaxel and cisplatin-based HIPEC and assessed hospital stay and 90-day outcomes; because it was single-arm and phase II, it should not be interpreted as comparative evidence against open cytoreduction. [152]
For remnant gastric cancer, a systematic review and meta-analysis compared subtotal gastrectomy with conventional completion total gastrectomy, focusing on safety, feasibility, morbidity, and oncologic adequacy. The evidence remains limited because this is an uncommon condition and the optimal extent of resection is not established by the cited review. [86]C4
| Domain | Evidence-supported consideration |
|---|---|
| Port strategy | Randomized comparison of 4-arm + 1-port versus 3-arm + 2-port robotic distal gastrectomy. [33]A1b |
| Pancreatic complications | Evaluate left gastric vein anatomy and minimize pancreatic contact during suprapancreatic dissection. [93]C4[94]B3b |
| Anastomotic complications | Reconstruction-specific techniques and early CT evaluation have been studied, but evidence is procedure-specific. [95]C4[138] |
| Infection | Follow patients for 30 days and consider healthcare-associated infections beyond surgical-site infection. [150]C |
| VTE | Risk is increased by older age, prior VTE, thrombophilia, low albumin, and transfusion. [154] |
| Patient resilience | Use prehabilitation, frailty/sarcopenia assessment, inflammatory-metabolic indices, and metabolic monitoring. [83]A1b[89]B2b[91]C4[151] |
Postoperative Recovery and ERAS
- ▸ERAS reduces complications, hospital stay, and improves survival in stage III.
- ▸Avoid routine abdominal drains but consider selective omission.
Enhanced Recovery After Surgery (ERAS) is standard for surgery. Meta-analysis of 13 RCTs (n=1,915) shows ERAS shortens hospital stay (MD -1.82 days), reduces complications (OR 0.63), and accelerates flatus, oral intake, and ambulation [102]A1a. Key elements: prehabilitation for frail elderly (Geriatric 8 ≤14) reduces 30-day complications from 28.7% to 17.2% [107]A1b; multimodal opioid-sparing analgesia (subcostal TAP block, acetaminophen, COX-2 inhibitors) reduces fentanyl consumption by 500 μg over 72 hours [109]A1b; early oral feeding is safe [104]A1a; avoid routine abdominal drains (reduces complications, OR 0.53) [118]A1a, but selective omission is prudent (ADIGE: increased reoperation from 7.7% to 15%) [111]A1b. The GISSG1901 trial showed ERAS improves 3-year OS (86.56% vs. 80.11%) and DFS in stage III disease [110]A1b. Pearl: ERAS is not merely about faster discharge, the GISSG1901 trial showed it improves 3-year survival in stage III gastric cancer (NNT ≈ 7 to prevent one death), likely through reduced complications, attenuated inflammation, and earlier adjuvant chemotherapy [110]A1b.
| Component | Evidence Summary | Key Reference |
|---|---|---|
| Prehabilitation (frail patients) | Reduces 30-day complications from 28.7% to 17.2% | [107]A1b |
| Multimodal opioid-sparing analgesia | Reduces pain scores and fentanyl consumption by 500 μg/72 h | [109]A1b |
| Early oral feeding | Reduces hospital stay by 1.82 days; safe without increased complications | [104]A1a |
| Avoidance of routine drainage | Faster recovery, fewer complications (OR 0.53); ADIGE trial shows increased reintervention risk | [118]A1a[111]A1b |
| Psychosocial intervention | Improves 2-year DFS (HR 0.58) and OS (HR 0.52) | [106]A1b |
Outcomes by Stage and Approach
- ▸Adjuvant SOX improves 3-year DFS in stage II-III (NNT=11).
- ▸Nivolumab+chemo for CPS≥5 yields 5-year OS benefit (NNT=10).
For resectable stage II-III, adjuvant SOX (S-1 + 130 mg/m² q3 weeks) for 6 months yields 3-year DFS 74.3% vs. 64.8% with S-1 alone (NNT=11) [73]A1b. Neoadjuvant DOS improves PFS (HR 0.70) [10]A1b. For advanced/metastatic disease, first-line + chemotherapy in PD-L1 CPS≥5 gives 5-year OS 16% vs. 6% (HR 0.71; NNT=10) [120]A1b. In HER2+ disease after trastuzumab failure, anbenitamab + chemo improves PFS (HR 0.25) and OS (HR 0.29) [121]A1b. MSI-high status predicts exceptional immunotherapy benefit (OS HR 0.34) [128]A1a. Laparoscopic vs. open gastrectomy shows equivalent oncologic outcomes: LOGICA trial reported 1-year OS 76% vs. 78%, R0 95% both, lymph node yield 29 both [16]A1b. Pearl: Nodal response (ypN0) after preoperative therapy is a stronger predictor of survival than primary tumor response; patients with ypN+ disease have poor outcomes regardless of postoperative therapy [79]B3b.
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Backlinks
- ← Gastric Cancer Palliative Care (Detailed)
- ← Gastric Cancer Radiation Management
- ← Gastric Cancer Radiation Management (Detailed)
- ← Gastric Cancer Surveillance and Follow-up
- ← Gastric Cancer Systemic Therapy (Detailed)
- ← Gastric Cancer (Detailed)
- ← Gastric Cancer Surveillance and Follow-up (Detailed)
- ← Gastric Cancer Recurrent and Metastatic Disease
- ← Gastric Cancer Recurrent and Metastatic Disease (Detailed)
- ← Gastric Cancer Palliative Care