Application value of lymph node-targeted chemotherapy in resection of the esophageal carcinoma: a prospective study / 中华消化外科杂志

ABSTRACT

Objective To investigate the application value of lymph node-targeted chemotherapy in resection of esophageal carcinoma.Methods The prospective study was conducted.The clinical data of 117 patients with middle and low esophageal carcinoma (without involving esophagogastric junction) who underwent left transthoracic esophagectomy and regional lymph node dissection in the West China Hospital of Sichuan University between January 2013 and December 2013 were collected.All patients were allocated into the 4 groups by semi-randomized control method:CPL group received intraoperatively carbon nanoparticles-paclitaxel for lymph node-targeted chemotherapy,CFL group received intraoperatively carbon nanoparticles-fluorouracil for lymph nodetargeted chemotherapy,FV group received preoperative fluorouracil intravenous chemotherapy,and control group underwent left transthoracic esophagectomy and regional lymph node dissection.CPL and CFL groupssuspensions of carbon nanoparticles and chemotherapy drugs were preoperatively prepared,and were intraoperatively injected under mucosa of lower edge of thoracic esophageal tumor using 0.1 mL syringes.FV groupfluorouracil with 100 mL of saline were mixed,and then were preoperatively injected by intravenous drip within 30 minutes.After cutting tissues of esophageal carcinoma,lymph nodes of left gastric arteria were removed,and drug level in lymph nodes was measured.At the beginning of esophagogastrostomy in the CPL,CFL and FV groups,3 mL peripheral venous blood were collected and measured for serum drug level.Control grouppatients underwent left transthoractic esophagectomy and regional lymph node dissection (no blood sample and esophageal specimen).Observation indicators(1) comparison of drug levels in lymph node and serum of patients with chemotherapy;(2) follow-up and survival4-year cumulative survival rate in 4 groups.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to December 2017.Measurement data with normal distribution and homogeneity of variance were represented as (x)±s,and comparisons among groups were analyzed using the ANOVA.Measurement data with skewed distribution were described as M (P25,P75),and comparisons among groups and between groups were respectively analyzed using the Kruskal-Wallis rank test and Mann-Whitney U test or Wilcoxon signed rank test.Comparisons of count data were analyzed using chi-square test or Fisher exact probability.Ordinal data were compared by the Kruskal-Wallis test.The survival curve was drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results One hundred and seventeen patients were screened for eligibility,including 90 males and 27 females,and age was 37-84 years old,with an average age of 62 years old.Of 117 patients,41,41,9 and 26 were respectively allocated into the CPL,CFL,FV and control groups.Eligible patients recovered and were discharged from hospital,without bone marrow depression,severe diarrhea,anastomotic leakage and severe pneumonia.(1) Comparison of drug levels in lymph node and serum of patients with chemotherapydrug levels in the CPL,CFL and FV groups were respectively 2.16 μg/g (1.14 μg/g,4.39 μg/g),0.44 μg/g (0.11 μg/g,1.18 μg/g),0.11 μg/g (0,0.28 μg/g) in lymph nodes and 0 (0,0),0 (0,0.31 μg/mL),0 (0,0.30 μg/mL) in serum.Drug levels of lymph node in the CPL and CFL groups were higher than those of serum,with statistically significant differences (Z=-5.579,-3.069,P＜0.05).There was no statistically significant difference in drug levels of lymph node and serum of FV group (Z =-0.365,P＞0.05).There was a statistically significant difference in drug levels of lymph node among CPL,CFL and FV groups (H=33.458,P＜0.05),and in drug levels of serum among CPL,CFL and FV groups (H=10.356,P＜0.05).Further analysis showed that fluorouracil level of lymph node in the CFL group was higher than that in the FV group,with a statistically significant difference (Z =82.500,P＜ 0.05),and there was no statistically significant difference in fluorouracil level of serum between CFL group and FV group (Z =160.500,P＞0.05).Paclitaxel level of lymph node in the CPL group was higher than fluorouracil level of lymph node in the CFL group,with a statistically significant difference (Z =351.000,P＜0.05),and paclitaxel level of serum in the CPL group was lower than fluorouracil level of serum in the CFL group,showing a statistically significant difference (Z=577.000,P＜0.05).(2) Follow-up and survivalof 117 patients,21 lost follow-up,and 96 were followed up for 6.0-58.0 months,with a median time of 20.0 months.The 4-year cumulative survival rate in the CPL,CFL,FV and control groups was respectively 46.2％,27.8％,33.3％ and 17.1％.There was no statistically significant difference in the survival of 4 groups (x2 =5.166,P＞0.05).Conclusions The lymph node-targeted chemotherapy can promote chemotherapy drugs to aggregate in the lymph nodes during resection of esophageal carcinoma.The affinity of chemotherapy drugs on carrier is involved in clinical effects,and single use of chemotherapy drug cannot improve postoperative survival rate of patients.