The seven-day cumulative post-esophagectomy inflammatory response predicts cancer recurrence

Abstract

Background: The relationship between postoperative cumulative systemic inflammation and cancer survival needs to be investigated. We developed an approach to the prognostication of postoperative esophageal cancer by establishing low and high cut-off values for the C-reactive protein (CRP) area under the curve (AUC) at 7 and 14 days after esophagectomy.

Methods: One hundred and twenty-five consecutive patients with biopsy-proven invasive esophageal squamous cell carcinoma (SCC) who underwent esophagectomies were evaluated. Postoperative CRP levels were analyzed for the first 14 days after surgery. The AUC on days 7 and 14 were calculated and compared with clinicopathological features and survival. The cut-off values for CRP at 7 days (CRP 7 d) and 14 days (CRP 14 d) were 599 mg/L and 1153 mg/L, respectively.

Results: The patients in the low CRP 7 d group had significantly better recurrence-free survival (RFS) and overall survival (OS), not that in the low CRP 14d group. The OS rates in the high CRP groups at PODs 1, 3, 10, and 14 were significantly lower than those in the low CRP groups. Postoperative complications were more common in the high CRP groups on PODs 3, 10, and 14. Univariate analyses revealed that pTNM stage, depth of tumor invasion, tumor location, lymph node involvement, and CRP 7 d were significant prognostic factors for both OS and RFS. The Cox proportional hazards model identified pTNM, tumor location, and CRP 7d as independent prognostic factors for the RFS and OS.

Conclusions: Early prediction of patients with postoperative complications, and adequate management will suppress the elevation of CRP 7 d and further suppress the CRP value in the late postoperative period, which may improve the prognosis of esophageal cancer patients after esophagectomy.

Keywords: CRP; Complications; Esophageal cancer; Esophagectomy; Prognosis.

Fig. 1

The patients flow diagram in this study

Fig. 2

The CRP values (mg/L) on postoperative days. The trendline was created by Microsoft EXCEL (Dotted line). After then, area under the trendline as calculated by integral calculus

Fig. 3

A Recurrence-free survival in the low and high CRP 7 d groups after esophagectomy. The low CRP 7 d group had significantly better survival than the high CRP 7 d group (P = 0.0117). B Overall survival between low and high CRP 7 d groups after esophagectomy. Low CRP 7 d group was significantly better survival than high CRP 7 d group (P = 0.0087)

Fig. 4

A Recurrence-free survival between low and high CRP 14 d groups after esophagectomy. Low CRP 14 d group was tendency to be better survival than high CRP 14 d group, but not significantly difference (P = 0.132). B Overall survival between low and high CRP 14 d groups after esophagectomy. Low CRP 14 d group tended to have better survival than the high CRP 14 d group, but not to a significant degree (P = 0.111)

Fig. 5

A Overall survival between with and without postoperative complications ≥ Grade 2. No significant differences between two groups (P = 0.668). B Recurrence free survival between with and without postoperative complications ≥ Grade2. No significant differences between two groups (P = 0.427)

Fig. 6

Postoperative CRP values for 14 days after surgery. The values are expressed as mean ± SD. Postoperative complications were more common in PODs3,10,14 (P = 0.0068, P = 0.0066, P = 0.00049)