Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study

Abstract

Background: Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship between LVI/PNI and survival of esophageal squamous cell carcinoma (ESCC) is still unclear. We aim to demonstrate the prognostic significance of LVI/PNI in ESCC.

Methods: A total of 195 ESCC patients underwent curative surgery from 2012 to 2018 was collected in the 2nd Affiliated Hospital of Fujian Medical University. All the patients were divided into four groups based on the status of the neurovascular invasion: (1) neither LVI nor PNI (V0N0); (2) LVI alone (V1N0); (3) PNI alone (V0N1); (4) combined LVI and PNI (V1N1). First, the analysis included the Kaplan-Meier survival estimates with the Log rank test were performed to determine median overall survival (OS) in different groups divided according to the clinical factor, respectively. And the association between OS with multi clinical factors was examined using Cox regression analysis. Next, the risk factors for recurrence in patients with V1N1 were analyzed with univariate and multivariate logistic regression analyses, respectively.

Results: The cases in V0N0, V1N0, V0N1, and V1N1 groups were 91 (46.7%), 62 (31.8%), 9 (4.6%) and 33 (16.9%), respectively. The OS in the four groups was different (P < 0.001). The 1-, 3- and 5-year OS in V0N0 group was higher than that in V1N1 group, respectively (1-year OS: 93.4% vs 75.8%, 3-year OS: 53.8 % vs 24.2%, 5-year OS: 48.1% vs 10.5%). The OS in stage I-II for patients with V1N1 was significantly lower than that in the other groups (V0N0, V1N0, V0N1) (P < 0.001). The postoperative adjuvant chemotherapy was a significant impact factor of OS for ESCC patients with V1N1 (P = 0.004). Lymphatic invasion and LVI were significantly prognosis factors associated (P = 0.036, P = 0.030, respectively). The ulcerative type is a risk factor for V1N1 occurance (P = 0.040).

Conclusions: The LVI and PNI are important prognosis factors for ESCC patients. ESCC patients with simultaneous lymphangio vascular and perineural invasion (V1N1) showed worse OS than patients with either lymphangio vascular or perineural invasion alone (V1N0 or V0N1) or none (V0N0). In addition, adjuvant chemotherapy may prolong the OS for ESCC patients with V1N1.

Keywords: Esophageal squamous cell carcinoma; Lymphangio vascular invasion; Overall survival; Perineural invasion; Prognosis.

Figure 1. Microscopic features of four pathological patterns.

Pathological section of ESCC with four histological characteristics stained with hematoxylin and eosin: (A) neither LVI nor PNI (V0N0); (B) only LVI (V1N0); (C) only PNI (V0N1); (D) combined LVI and PNI (V1N1).

Figure 2. The prognosis of patients was determined in specific situation compared in subgroups.

The prognosis of patients was determined in the four groups compared in subgroups (pathological stage, status of lymphatic invasion and pathological depth of tumor invasion). (A) Stage I–II P < 0.001; (B) Stage III–IV P > 0.05; (C) Ly (−) P = 0.005; (D) Ly (+) P > 0.05; (E) T1–2 P < 0.001; (F) T3–4 P = 0.008.

Figure 3. Comparison of Kaplan–Meier curves stratified by whether postoperative adjuvant chemotherapy.

Comparison of Kaplan–Meier curves stratified by whether postoperative adjuvant chemotherapy. (A) V0N0 P = 0.109; (B) V1N0 P = 0.933; (C) V0N1 P = 0.153; (D) V1N1 P = 0.004.

Figure 4. Prognostic factors.

(A–E) The prognostic impact of sex, stage, lymphatic invasion status and pattern of LVI and PNI on overall survival (OS). (F) Mean survival analysis time in four pathological types, (G) the value of statistically significant variables for ESCC patients with V1N1.