Safety And Efficacy Of Prophylactic Hyperthermic Intraperitoneal Chemotherapy For Gastric Cancer

Objective:To determine the safety and efficacy of prophylactic hyperthermic intraperitoneal chemotherapy(HIPEC)for gastric cancer.Methods:Our study include two parts.The first part is a retrospective study.Patients with gastric caner that had undergone surgery between January 1,2016 and December 31,2019 were divided into HIPEC group and control group according to inclusion and exclusion criteria.Then,we analyzed the complications rate,recurrence rate and overall survival(OS)between two groups,and risk factors for recurrence and OS.The second part is a systematic review and meta analysis.We searched foreign database and Chinese database to find prophylactic HIPEC for gastric cancer.Then,we analyzed the quality of included studies,and pooled the results of incidence of complications,recurrence rate and overall survival rate.Results:The first part,in our retrospective study,163 gastric cancer patients were included and divided into HIPEC group(n=48)and control group(n=115).The baseline data including age,sex,comorbidities,the location of tumor,tumor stage,histology grade,and the value of gastrointestinal tumor biomarkers were comparable between HIPEC and control group.The time to postoperative first liquid intake was 4.87 days in HIPEC group and 4.6 days in control group.The postoperative hospital stay was 9.58 days in HIPEC group and 9.07 days in control group.There were no significant difference in the time to first liquid intake and postoperative hospital stay between HIPEC group and control group.There were no significant difference as to the incidence of other complications:fever(10.4%vs 7%,p=0.528);anastomotic leakage(2.1%vs 0.9%,p=0.504);ileus(4.2%vs 1.7%,p=0.582);wound infection(2.1%vs 1,7%,p=1);mortality within 30 days(2.1%vs 0.9%,p=0.504);re-operation within 30 days(2.1%vs 1.7%,p=1);hepatic toxicity side effects(6.2%vs 4.3%,p=0.694);renal toxicity side effects(2.1%vs 0%,p=0.694);respiratory dysfunction(2.1%vs 0.9%,p=0.504).The recurrence rate in the HIPEC group was equal to that in the control group.1-year recurrence were comparable between HIPEC group and control group(11.6%vs 12.9%,p=0.836).There were also no significant difference in 2-year recurrence(20.9%vs 22.8%,p=0.808),and 3-year recurrence(27.9%vs 22.8%,p=0.511).Univariate and multivariate logistic regression analysis showed that N stage was related with recurrence.As to OS rate,there were no significant difference in 1-year OS(88.4%vs 84.2%,p=0.563),2-year OS(86%vs 76.2%,p=0.194),and 3-year OS(83.7%vs 72.3%,p=0.226).Univariate and multivariate Cox regression analysis showed that N stage and preoperative value of CA19-9 were related with OS.The second part,in our systematic review and meta analysis,a total of 1725 gastric cancer patients from 17 studies were analyzed.HIPEC had no significant influence on postoperative complications such as anastomotic leakage(RR=0.95,95%CI,0.45-2.21;p=0.98),ileus(RR=0.72,95%CI,0.34-1.53;p=0.4),duodenal stump leakage(RR=1.17,95%CI,0.34-4.06;p=0.8),wound infection(RR=1.02,95%CI,0.45-2.30;p=0.96),bone marrow suppression(RR=1.16,95%CI,0.86-1.57;p=0.34).HIPEC had no significant influence on 1-year recurrence(RR=0.87,95%CI,0.45-1.71;p=0.69).HIPEC decreased 3-year recurrence(RR=0.45,95%CI,0.32-0.64;p<0.00001),5-year recurrence(RR=0.48,95%CI,0.30-0.77;p=0.002),and peritoneal recurrence(RR=0.45,95%CI,0.34-0.61;p<0.0001).As to OS,HIPEC prolonged 1-year OS(RR=0.64,95%CI,0.47-0.88;p=0.005),3-year OS(RR=0.625 95%CI,0.54-0.71;p<0.0001),and 5-year OS(RR=0.80,95%CI,0.70-0.92;p=0.001).Conclusions:Prophylactic HIPEC can be safely performed with no significant influence on all postoperative complications.The effect of prophylactic HIPEC on the long term prognosis depends on high quality randomized controlled studies with large sample size and clear outcome definition.HIPEC has a broad application prospect.The regime of HIPEC,especially the choice of drugs,requires further clinical studies to supply theoretical and technical support.