| Objective:In order to provide advices and references for the current applica-tion and development of enhanced recovery after surgery in the treatment of esoph-ageal cancer,the impacts on the recovery and prognosis of different choices of time to surgery after neoadjuvant therapy for esophageal cancer in enhanced recovery after surgery were analyzed by Meta analysis.Methods:Search strategy was formulated on the basis of“PICOS”principle and databases such as Pub Med,Web of Science,Cochrane Library and Embase were systematically searched,with the searching time limited from dates of establishment of these databases to November,2022.The subject terms included Enhanced recov-ery after surgery,Esophageal Neoplasms,Esophagectomy,Neoadjuvant Therapy,Time to Surgery and Time Interval.Relevant studies concerning the impacts of dif-ferent surgical time intervals after neoadjuvant therapy for esophageal cancer on the recovery and prognosis were collected,and were selected independently by two re-searchers based on strict inclusion and exclusion criteria.Eligible studies were in-corporated into Meta analysis and analyzed by the data extracted from them.Possi-ble disputes were resolved through negotiation.Review Manager 5.4 was used to complete Meta analysis.The effects of choosing different time to surgery on the postoperative recovery and prognosis of esophageal cancer patients were compared from multiple aspects,such as postoperative pathologic remission(PCR(Pathologic Complete Response),R0 resection and postoperative lymph node metastasis),peri-operative complications(postoperative anastomotic leakage,postoperative pulmo-nary complications,postoperative mortality within 30 and 90 days)and long-term survival(2-year and 5-year overall survival).Results:A total of 1349 literatures were retrieved,and 20 studies were included in the Meta-analysis after exclusion.The whole sample of 32422 patients coming from multiple countries and regions,with the tissue types including esophageal squa-mous cell carcinoma and adenocarcinoma,were collected and summarized.The studying time of these studies spanned from 2010 to 2021.All these included studies contained high quality according to NOS scores.Each study included into Meta anal-ysis was divided into shorter interval group(surgery within 6-8 weeks after Neoad-juvant therapy)and longer interval group(surgery beyond 6-8 weeks after Neoadju-vant therapy)with the cut-off point setting on 6-8 weeks.The results were as follows:(1)For PCR,15 studies were included,Q-test:P=0.03,I~2=44%<50%,heteroge-neity was huge,and random effects model was used.Overall OR=1.15,95%CI=[1.01,1.29],P<0.05,There was statistical significance between two groups,and better PCR could be obtained by delaying the time to surgery.(2)For R0 resec-tion,13 studies were included,with Q test:P=0.01,I~2=54%>50%and heteroge-neity was huge.Random effects model was used therefore.Overall OR=0.82,95%CI=[0.67 to 1.00],P=0.05,the discrepancy was statistically significant.The rate of R0 resection in the shorter interval group was significantly lower than it in the longer interval group.(3)For postoperative lymph node metastasis,13 studies were included,Q-test:P=0.09,I~2=37%<50%,heterogeneity was acceptable,and fixed effects model was used.Overall OR=0.90,95%CI=[0.84,0.96],P<0.05.There was statistical significance between two groups,and the probability of lymph node me-tastasis after neoadjuvant therapy was lower in the delayed surgery group than in the shorter interval group.(4)For postoperative anastomotic leakage,10 studies were included.Q test P=0.47,I~2=0%<50%.No obvious heterogeneity was found be-tween studies,and fixed effects model was used.Overall OR=1.20,95%CI=[1.00,1.43],P=0.05,difference was statistically apparent.Delaying the time to surgery after neoadjuvant therapy could increase probability of perioperative anastomotic leakage.(5)For postoperative pulmonary complications,seven studies were included,Q test P=0.08,I~2=48%<50%,heterogeneity was acceptable,and fixed effects model was used.Overall OR=1.50,95%CI=[1.17,1.92],P<0.05,and difference was statistically apparent.Probability of postoperative pulmonary complications could increase for delaying the time interval between neoadjuvant therapy and surgery.(6)For postoperative mortality within 30 days,9 studies were included.Q test P=0.74,I~2=0%<50%.No obvious heterogeneity was found,and fixed effects model was used.Overall OR=1.47,95%CI=[1.20,1.80],P<0.05,dif-ference was statistically apparent.For postoperative mortality within 90 days,5 stud-ies were included.Q test P=0.81,I~2=0%<50%.No obvious heterogeneity was found,and fixed effects model was used.Overall OR=1.42,95%CI=[1.20,1.69],P<0.05,difference was statistically apparent.Early surgical treatment after neoad-juvant therapy has significant advantages in reducing postoperative mortality within30 days and 90 days of esophageal cancer.(7)For 2-year OS,15 studies were in-cluded.Q test P=0.70,I~2=0%<50%.No obvious heterogeneity was found,and fixed effects model was used.Overall OR=0.83,95%CI=[0.76,0.89],P<0.05,dif-ference was statistically apparent.For 5-year OS,14 studies were included.Q test P=0.63,I~2=0%<50%.No obvious heterogeneity was found,and fixed effects model was used.Overall OR=0.81,95%CI=[0.74,0.89],P<0.05,difference was statistically apparent.Surgery within shorter interval after neoadjuvant therapy helps patients with esophageal cancer gain significant benefit in OS at 2 and 5 years.(8)No potential factors for heterogeneity was found by subgroup analyses and no vari-ational outcomes occurred after sensitivity analyses.There was no obvious publica-tion bias among the included studies.Conclusions:Delaying time to surgery after neoadjuvant therapy for esopha-geal cancer results in better PCR and less lymph node metastasis while surgery within shorter interval does better in R0 resection.In terms of perioperative compli-cations,early surgery could effectively reduce the occurrence of serious complica-tions such as anastomotic leakage,postoperative pulmonary complications and peri-operative mortality,promote the enhanced recovery after surgery,and improve the medical quality of patients.For long-term survival,early surgery results in better overall survival as well.In summary,it is recommended that patients with esopha-geal cancer should receive surgical treatment as soon as possible after neoadjuvant therapy to obtain great postoperative recovery and good quality of long-term sur-vival. |
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