Timing Matters: Optimizing Additional Surgery after Noncurative Endoscopic Submucosal Dissection in Early Gastric Cancer

Highlight

1. Additional surgery following noncurative endoscopic submucosal dissection (ESD) for early gastric cancer increases intraoperative burden compared to primary gastrectomy.
2. The timing interval between ESD and additional surgery significantly influences operative time and blood loss.
3. Delaying additional operation until approximately 35 days post-ESD is associated with a plateau in operation time and blood loss, suggesting an optimal timing window.
4. Earlier additional surgery (≤35 days) results in longer operations and greater blood loss compared to delayed surgery (>35 days).

Study Background

Early gastric cancer (EGC) is increasingly managed via endoscopic submucosal dissection (ESD), a minimally invasive procedure offering organ preservation and rapid recovery. However, when ESD is deemed noncurative—due to factors such as positive margins or lymphovascular invasion—additional surgery, typically gastrectomy, is recommended to achieve complete oncologic control. While ESD minimizes initial morbidity, supplemental surgery carries its own risks and challenges. The interval between noncurative ESD and subsequent gastrectomy may impact surgical complexity and patient outcomes, but optimal timing remains uncertain. Understanding how operation timing after noncurative ESD affects perioperative outcomes is critical for balancing surgical risks and benefits, optimizing patient recovery, and guiding clinical decision-making in early gastric cancer management.

Study Design

This retrospective study analyzed patients at a high-volume center with early gastric cancer undergoing surgical management between defined dates. Two cohorts were included: 135 patients who underwent additional gastrectomy following noncurative ESD (additional-operation group) and 582 patients who underwent primary gastrectomy without prior ESD (operation-only group). The study examined intraoperative outcomes—operation time, blood loss, and postoperative inflammatory markers—comparing these two groups.

Within the additional-operation group, the researchers used restricted cubic spline regression to explore the nonlinear relationship between the interval from ESD to subsequent surgery (measured in days) and intraoperative outcomes. A prespecified slope-based criterion identified the onset of plateau effects, guiding definition of early (≤35 days) versus late (>35 days) additional surgery subgroups for clinically interpretable comparisons.

Key Findings

Compared to primary gastrectomy patients, those undergoing additional surgery after ESD experienced significantly longer operative times (240.74 ± 60.44 minutes vs 226.43 ± 57.34 minutes; P = .010) and increased intraoperative blood loss (59.33 ± 26.24 mL vs 39.15 ± 18.43 mL; P < .001). Furthermore, postoperative inflammatory marker abnormalities were more frequent in the additional-operation group, indicating a heightened inflammatory response or surgical stress.

Restricted cubic spline analyses revealed a nonlinear association between the time interval from ESD to additional surgery and operative outcomes. Notably, operation time and blood loss decreased as the interval increased, reaching a plateau at approximately 35 days. This plateau suggests a threshold beyond which delaying surgery confers no further intraoperative benefit.

When the additional-operation group was divided by timing, the earlier-operation subgroup (≤35 days) had significantly longer operation times (252.69 ± 64.20 minutes) and more blood loss (72.84 ± 26.79 mL) compared to the late-operation subgroup (>35 days), which had operation times of 228.97 ± 54.43 minutes and blood loss of 45.88 ± 17.38 mL (P = .022 and P < .001, respectively). This indicates that postponing surgery beyond five weeks post-ESD may reduce perioperative risks.

Expert Commentary

The study provides valuable insights into surgical timing that could influence clinical guidelines on managing noncurative ESD in early gastric cancer. The increased complexity and inflammatory response associated with early additional surgery may reflect postoperative tissue changes such as edema, inflammation, fibrosis, or altered vascularity, which can increase surgical difficulty and bleeding risk if operations are performed prematurely.

These findings underscore the importance of individualized clinical decision-making. While oncologic urgency must be balanced, a delay of approximately five weeks may allow resolution of acute inflammatory changes, facilitating safer and more efficient surgery. Nonetheless, prospective studies are warranted to validate these results and assess long-term oncologic outcomes related to varied timing of additional surgery.

Limitations include the retrospective design and potential selection biases inherent in observational studies. The generalizability to diverse clinical settings and patient populations requires cautious interpretation. Additionally, the optimal timing must consider cancer progression risk, patient comorbidities, and institutional resources.

Conclusion

Additional gastrectomy after noncurative endoscopic submucosal dissection in early gastric cancer is associated with increased intraoperative burden compared to primary surgery. This study identifies a critical timing threshold—approximately 35 days post-ESD—beyond which operation time and blood loss decline and stabilize. This suggests that delaying additional surgery beyond this period may optimize perioperative outcomes by reducing surgical complexity and physiological stress. These findings inform multidisciplinary treatment planning and highlight the need for balanced approaches that incorporate surgical safety without compromising oncological efficacy.

Future prospective trials should evaluate standardized timing protocols and integrate oncological outcomes to establish evidence-based guidelines for the timing of additional operations following noncurative ESD in early gastric cancer.