Infrapyloric Lymph Node Metastasis Pattern in Middle/Lower Gastric Cancer

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Infrapyloric Lymph Node Metastasis Pattern in Middle/Lower Gastric Cancer: An Exploratory Analysis of a Multicenter Prospective Observational Study (IPA-ORIGIN)

Gastric cancer remains a significant health burden in China, particularly affecting the middle and lower regions of the stomach. Among the critical determinants of prognosis and treatment strategy is the metastatic behavior of infrapyloric lymph nodes (No. 6 lymph nodes). This study, derived from the Infrapyloric Artery Origin (IPA-ORIGIN) prospective multicenter observational trial, investigates the metastasis patterns and risk factors associated with No. 6 lymph node involvement in middle/lower gastric cancer. The findings aim to refine clinical decision-making regarding lymphadenectomy and surgical margins.

Study Design and Patient Cohort

The IPA-ORIGIN study (ClinicalTrials.gov identifier: NCT03071237) was conducted across 34 gastrointestinal surgery centers in China, enrolling 429 patients between 2017 and 2020. After excluding 39 cases due to non-malignant postoperative pathology or inappropriate gastrectomy, 385 patients were analyzed. Among these, 181 cases with available distal resection margin (DRM) and No. 6 lymph node grouping data formed the core cohort for this exploratory analysis: 120 underwent distal gastrectomy, and 61 underwent total gastrectomy. Rigorous surgical quality control measures were enforced, including photo or video documentation of the No. 6 lymph node dissection area to ensure standardization.

Pathological Evaluation and Data Collection

Lymph nodes were meticulously dissected, categorized, and examined histopathologically. The median number of total lymph nodes retrieved per patient was 32.9, with 3.5 nodes specifically from the No. 6 station. Metastasis to the No. 6 lymph node was identified in 22.5% (27/120) of distal gastrectomy patients. Stratification by T-stage revealed a metastasis rate of 12.7% (7/55) in T1 tumors and 30.8% (20/65) in T2–T4a tumors.

Key Risk Factors for No. 6 Lymph Node Metastasis

Univariate analysis identified five significant risk factors:

  1. Tumor size ≥2 cm: Metastasis rate of 27.4% vs. 4.0% in smaller tumors (RR: 9.043; 95% CI: 1.164–70.291; P=0.035).
  2. Neural infiltration: 34.1% metastasis rate in positive cases vs. 16.5% in negative cases (RR: 2.632; 95% CI: 1.094–6.332; P=0.031).
  3. Vascular infiltration: 35.7% metastasis rate in positive cases vs. 15.4% in negative cases (RR: 3.056; 95% CI: 1.266–7.376; P=0.013).
  4. Advanced T-stage (T2–T4a): 30.8% metastasis rate vs. 12.7% in T1 tumors (RR: 3.048; 95% CI: 1.176–7.896; P=0.022).
  5. DRM ≤3 cm: A progressive decline in metastasis rates correlated with increasing DRM. For DRM ≤1 cm, the metastasis rate was 72.7%, dropping to 8.3% for DRM >6 cm (RR: 4.121; 95% CI: 1.630–10.421; P=0.003).

Multivariate analysis confirmed tumor size ≥2 cm (RR: 8.079; 95% CI: 1.016–64.227; P=0.048) and DRM ≤3 cm (RR: 3.831; 95% CI: 1.485–9.884; P=0.006) as independent predictors of No. 6 lymph node metastasis. Notably, histological differentiation type did not correlate with metastasis risk.

Clinical Implications of DRM and Tumor Location

The distal resection margin emerged as a critical factor. In tumors located ≤3 cm from the pylorus, the No. 6 lymph node metastasis rate was 25.2% (27/107), compared to 0% in cases with DRM >6 cm. This gradient underscores the anatomical proximity’s role in lymphatic spread. For early-stage (T1) tumors, seven cases exhibited No. 6 metastasis, all with an average tumor diameter of 3 cm. This challenges the assumption that early-stage tumors inherently pose a lower metastatic risk and highlights the necessity of No. 6 lymphadenectomy even in select T1 cases.

Comparison with Prior Evidence

Previous retrospective studies reported No. 6 metastasis rates of 18.7% in lower gastric cancer and 1.9% in upper gastric cancer. However, these studies faced criticism for inconsistent lymphadenectomy protocols. The IPA-ORIGIN study’s prospective design and standardized dissection protocols enhance the reliability of its findings. For instance, Kong et al. (2009) reported a 15.2% metastasis rate in patients with DRM <6 cm, lower than the 25.2% observed here. This discrepancy may stem from differences in cohort composition, as the current study included more advanced-stage tumors.

Technical Considerations in Lymphadenectomy

The infrapyloric artery’s anatomical variability was a secondary focus of the parent IPA-ORIGIN trial. Precise identification and preservation of this artery during dissection are crucial to avoid postoperative complications while ensuring thorough lymph node removal. The study’s emphasis on photographic/video documentation provided an additional layer of quality assurance, reducing inter-surgeon variability.

Recommendations for Surgical Practice

  1. Tumor Size and Resection Margins: For tumors ≥2 cm or with DRM ≤3 cm, complete No. 6 lymphadenectomy is strongly recommended, irrespective of T-stage.
  2. Early Gastric Cancer: Pylorus-preserving gastrectomy should be avoided in T1 tumors exceeding 2 cm or located near the pylorus due to the non-negligible metastasis risk.
  3. Advanced T-Stage: In T2–T4a tumors, the high metastasis rate (30.8%) necessitates aggressive lymph node dissection, even with DRM >3 cm.

Limitations and Future Directions

While the study’s prospective design strengthens its conclusions, the analysis was limited to middle/lower gastric cancers, excluding proximal tumors. Furthermore, the cohort’s geographic restriction to China warrants validation in diverse populations. Future research should explore molecular markers predictive of lymphatic spread and assess long-term survival outcomes tied to No. 6 lymphadenectomy completeness.

Conclusion

This multicenter analysis establishes tumor size ≥2 cm and DRM ≤3 cm as independent risk factors for No. 6 lymph node metastasis in middle/lower gastric cancer. These findings advocate for tailored surgical strategies, prioritizing thorough No. 6 lymph node dissection in high-risk cases to optimize oncological outcomes.

doi.org/10.1097/CM9.0000000000000995

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