Timing of hepatectomy for resectable synchronous colorectal liver metastases: for whom simultaneous resection is more suitable--a meta-analysis

Abstract

Background: The optimal timing of resection for synchronous colorectal liver metastases is still controversial. Retrospective cohort studies always had baseline imbalances in comparing simultaneous resection with staged strategy. Significantly more patients with mild conditions received simultaneous resections. Previous published meta-analyses based on these studies did not correct these biases, resulting in low reliability. Our meta-analysis was conducted to compensate for this deficiency and find candidates for each surgical strategy.

Methods: A systemic search for major databases and relevant journals from January 2000 to April 2013 was performed. The primary outcomes were postoperative mortality, morbidity, overall survival and disease-free survival. Other outcomes such as number of patients need blood transfusion and length of hospital stay were also assessed. Baseline analyses were conducted to find and correct potential confounding factors.

Results: 22 studies with a total of 4494 patients were finally included. After correction of baseline imbalance, simultaneous and staged resections were similar in postoperative mortality (RR = 1.14, P = 0.52), morbidity (RR = 1.02, P = 0.85), overall survival (HR = 0.96, P = 0.50) and disease-free survival (HR = 0.97, P = 0.87). Only in pulmonary complications, simultaneous resection took a significant advantage (RR = 0.23, P = 0.003). The number of liver metastases was the major factor interfering with selecting surgical strategies. With >3 metastases, simultaneous and staged strategies were almost the same in morbidity (49.4% vs. 50.9%). With ≤3 metastases, staged resection caused lower morbidity (13.8% vs. 17.2%), not statistically significant.

Conclusions: The number of liver metastases was the major confounding factor for postoperative morbidity, especially in staged resections. Without baseline imbalances, simultaneous took no statistical significant advantage in safety and efficacy. Considering the inherent limitations of this meta-analysis, the results should be interpret and applied prudently.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Study search process.

Figure 2. Pooled postoperative morbidity.

Forest plots displayed the results of the meta-analysis comparing postoperative complication morbidity following simultaneous resection vs. staged resection for SCRLMs. M-H: Mantel-Haenszel method. Fixed: The heterogeneity test showed no significant heterogeneity, and fixed effect model was used. CI: confidence interval. Favours Simultaneous: With results on this side, simultaneous group had lower postoperative mortality. Favours Staged: With results on this side, staged group had lower postoperative mortality.

Figure 3. Subtype analyses of pooled postoperative morbidity.

Forest plots displayed the results of the meta-analysis comparing overall survival following simultaneous resection vs. staged resection for SCRLMs. IV: Inverse Variance method. Fixed: The heterogeneity test showed no significant heterogeneity, and fixed effect model was used. CI: confidence interval. Favours Simultaneous: With results on this side, simultaneous group had longer overall survival. Favours Staged: With results on this side, staged group had longer overall survival.

Figure 4. Pooled analyses of baseline imbalances.

Forest plots displayed the potential confounding factors found by baseline analyses. M-H: Mantel-Haenszel method. IV: Inverse Variance method. Random: In some subgroups there were significant heterogeneity, and random effect model was used. CI: confidence interval. A) Baseline analysis on number of liver metastases. Staged/Sim. favours lower: more patients in staged/simultaneous group had lower number of metastases. B) Baseline analysis on size of liver metastases. Staged/Sim. favours small: more patients in staged/simultaneous group had smaller size of metastases. C) Baseline analysis on distribution of liver metastases. Staged/Sim. faours unilobar: more patients in staged/simultaneous group had unilobar liver metastases. D) Baseline analysis on scope of hepatectomy. Staged/Sim. favours minor: more patients in staged/simultaneous group received minor hepatectomy. E) Baseline analysis on primary tumor location. Staged/Sim. favours right-sided: more patients in staged/simultaneous group had primary tumor located at right-sided colon.

Figure 5. Subgroup analyses in terms of postoperative morbidity.

Forest plots displayed the subgroup analyses in terms of postoperative morbidity. Studies with significant baseline imbalances were compared with studies without baseline imbalances. The shaded area between vertical dotted lines represented the overlap regions of the 95% confidence interval of the pooled results between each subgroup. M-H: Mantel-Haenszel method. Fixed: The heterogeneity test showed no significant heterogeneity, and fixed effect model was used. CI: confidence interval. Favour simultaneous/staged: Simultaneous/Staged group had lower postoperative morbidity. A) Subgroup analysis on number of liver metastases. B) Subgroup analysis on size of liver metastases. C) Subgroup analysis on distribution of liver metastases. D) Subgroup analysis on scope of hepatectomy. E) Subgroup analysis on primary tumor location.