many studies have demonstrated that surgery can promote cancer metastasis by suppressing immunity and natural killer ( nk ) cell activity , both in vivo and in vitro   morphine- or fentanyl - based general anesthesia elicits an immunosuppressive effect by decreasing nk cell activity . epidural anesthesia decreases the stress response after surgery , which can promote tumor metastasis [ 79 ] . administration of opioids and inhaled anesthetics also contributes to increased nk cell activation during neural blockade . however , other studies found no association between anesthesia ( epidural and non - epidural experimental groups ) and survival or the recurrence of cancer after cancer surgery . in another study , epidural anesthesia was associated with a lower recurrence of cancer after cancer surgery in patients older than 64 years . in a large cohort study , epidural anesthesia was associated with prolonged survival in cancer patients without metastasis ; however , recurrence in these patients was unaffected . therefore , due to the conflicting results , we retrospectively analyzed 273 patients who underwent gastric cancer surgery . after we received approval from the review board and ethics committee of zhejiang cancer hospital , we collected the clinical records of 273 patients who underwent primary gastric cancer resection between august 2006 and december 2010 . the follow - up ended at death , and the longest follow - up period lasted nearly 8 years ( september 2006 to september 2014 ) . in total , 116 patients were in the non - epidural group , and 157 patients were in the epidural - supplemented group . epidural anesthesia was administrated in gastric cancer patients except for those with low blood volume , shock , local infection / surgery / trauma / malformation , bacteremia that may cause epidural infection , low coagulation status or insufficient stopping time anticoagulant , children , mental illness , and patients who refused the epidural . general anesthesia was induced with 0.5 g / kg sufentanil ( yichang humanwell pharmaceutical co. ltd . yichang , hubei , china ) 1.33.0 mg / kg propofol ( astrazeneca , uk ) , and 3050 g / kg midazolam in patients of both groups . anesthesia was maintained with 412 mg / kg propofol and 0.51.0 g / kg remifentanil in the non - epidural group . yichang , hubei , china ) was replaced with 0.25% levobupivacaine ( rundu , zhuhai , china ) or ropivacaine ( astrazeneca , uk ) via an epidural catheter in the epidural group . these factors included age , sex , asa class , tumor stage , anesthetic technique , surgical method , hemorrhage volume during the operation , and radiotherapy with or without chemotherapy , as well as a history of hypertension , diabetes , coronary heart disease , chronic obstructive pulmonary disease , liver disease , or any other disease . the tnm ( topography , lymph node , and metastasis ) staging was also obtained , and the tumors were divided into stages 0iv based on the pathologic staging system that was in use when the surgery was originally performed . the data were recorded in excel , and spss statistical analysis software was the main tool used for data analyses . normally distributed continuous variables were compared using independent - samples t tests . we used the kaplan - meier log - rank test for univariate analyses and the cox proportional hazards regression model for multivariate analyses of the survival time after cancer surgery . all factors that affect survival time after cancer surgery were selected as the main effects in the multivariate cox model . all baseline factors , including perioperative and postoperative risk factors , were compared between the groups ( table 1 ) . the median survival times for cancer patients were 13.15 ( 7.121.95 ) and 13.2 ( 7.823.0 ) months for patients in the non - epidural and epidural - supplemented groups , respectively . the kaplan - meier analysis indicated no association between epidural - supplemented anesthesia and prolonged survival ( p=0.680 log - rank ) , as shown in figure 1 . however , epidural anesthesia increased the long - term survival in patients younger than 65 years ( p=0.035 log - rank test ) ( figure 2 ) . the multivariate cox regression model indicated no significant association between epidural use and prolonged survival after cancer surgery ( p=0.522 ) , and the adjusted estimated hazard ratio was 0.919 ( 95% ci 0.711.19 ) ( table 2 ) . asa status , tumor clinical stage , and chemoradiotherapy still affected prolonged survival after gastric cancer surgery . currently , whether epidural anesthesia prolongs the survival of cancer patients after surgery is controversial . biki , and hiller   demonstrated that epidural use is associated with lengthened survival in patients receiving surgery for prostatic carcinoma , pancreatic adenocarcinoma , and gastro - esophageal cancer . in contrast , studies by christopherson   and myles   showed no association between epidural anesthesia and prolonged survival in patients receiving surgery for gastric , colorectal , gastro - esophageal , non - small cell lung , and abdominal cancers . a cochrane review addressing this topic showed no survival benefit for the 2 groups by using a fixed - effects model with an hr of 1.03 ( 95% ci 0.861.24 ) in the pooled results . in recent decades , scientists have focused on the effects of perioperative factors and interventions on cancer recurrence and overall survival . many factors are involved in cancer recurrence and overall survival , including tumor type , tumor stage and size , surgical skill and techniques , anesthetic technique , radiotherapy with or without chemotherapy , blood loss , and transfusions during the perioperative period . other factors include comorbid diseases , such as hypertension , immunodeficiency , diabetes , or chronic obstructive pulmonary disease . the stress of surgery negatively affects the adaptive immune system . because immune surveillance is the first indicator for preventing cancer metastasis , immune suppression or disturbance may decrease the defensive barrier against intruders such as tumor cells , as well as inflammation . immune suppression may then facilitate cancer cell migration and lead to cancer recurrence at either a local or distant site . the suppression of nk cell activity due to the stress of surgery promotes tumor movement [ 1720 ] . some anesthetics such as opioids and inhaled anesthetics may inhibit immune function , including nk cell activity , lymphocyte proliferative responses to mitogens , and phagocytic activity . morphine and fentanyl have been well studied for their ability to suppress nk cell cytotoxicity . as previously described , the limited use of opioids during local anesthesia may attenuate the suppression of nk cell cytotoxicity . additionally , regional anesthesia inhibits the surgical stress response and is linked to earlier recovery times by reducing the incidence of thromboembolic , pulmonary , and gastrointestinal complications , as well as inflammation after major surgery . the conclusion of this study is consistent with that reached by cakmakkaya   that epidural anesthesia is not associated with the overall survival of gastric cancer patients after surgery . hiller   found that effective epidural analgesia improved the estimated median time to death among participants who received surgery for gastro - esophageal cancer . this study focused on gastric cancer patients who underwent surgery at the same hospital , and the study end - point was death . interestingly , we found that epidurals improved the long - term survival of younger patients ( aged 65 years or younger ) . because of the complex effects involved , we still have not reached a conclusion concerning the direct interaction between epidural use and prolonged survival after gastric cancer surgery . the beneficial effect observed in younger patients may be attributed to their education level , better health , and better immunity , or the administration of postoperative chemotherapy with or without radiotherapy . the majority of gastric cancer surgeries were performed in less than 2 hours in our hospital . fluid infusion during the surgery was continuous with a crystal : colloid ratio of 2 : 1 during a period of 2 hours . the outcomes for cancer patients can be influenced by many factors ( described above ) . retrospective studies have inherent weaknesses , including susceptibility to bias , selection bias , and confounding variables . also , the non - epidural group may have received other analgesics , which would increase the heterogeneity of the group . this retrospective study was unable to demonstrate any significant benefit for survival after the administration of epidural anesthesia during gastric cancer surgery . more results from randomized controlled trials , such as studies sponsored by the cleveland clinic , are needed to draw a reliable conclusion . according to the results of the mann - whitney u test , the median survival after surgery for patients receiving epidural anesthesia was 17.1 months ( range , 10.052.8 months ) . epidural anesthesia combined with general anesthesia during gastric cancer surgery had no effect on the long - term survival according to the cox proportional hazards regression model .
backgroundwhether regional anesthesia is associated with tumor - free and long - term survival is controversial . here , we focused on whether epidural anesthesia affects the long - term survival of gastric cancer patients after surgery.material/methodswe obtained the records of 273 patients undergoing gastric cancer surgery between august 2006 and december 2010 . 
 all patients received elective surgery , and the end - point was death . 
 the general anesthesia group comprised 116 patients and the epidural - supplemented group comprised 157 patients . 
 the results were analyzed using a multivariable model to determine the relationship between epidural use and long - term survival.resultsno obvious association was detected between epidural use and long - term survival according to the cox model ( p=0.522 ) ; the adjusted estimated hazard ratio was 0.919 ( 95% ci 0.711.19 ) . 
 however , according to kaplan - meier analysis , epidural anesthesia was associated with long - term survival among younger patients ( age up to 64 ) ( p=0.042 , log - rank ) ( but not among older patients ( p=0.203 , log - rank ) . a lower american society of anesthesiologists ( asa ) class and less chemoradiotherapy exposure were also associated with a longer survival . however 
 , advanced tumor stage still has a significant negative impact on survival.conclusionsno obvious difference was detected between the 2 anesthesia groups , but younger patients may benefit from epidural anesthesia .