Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat peritoneal carcinomatosis from gastric cancer

Abstract

Objective To study the efficacy and safety of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) to treat rabbit model of gastric cancer with peritoneal carcinomatosis (PC).Methods VX2 tumor cells were injected into the gastric submucosa of 42 adult male New Zealand rabbits using a laparotomic implantation technique,to construct rabbit model of gastric cancer with PC.The rabbits were randomly divided into three groups:control group (n = 14),CRS group (n = 14),and CRS + HIPEC group (n = 14 ).The rabbits in control group were observed for natural course of disease progression.Treatments were initiated 8 or 9 days after inoculation of tumor cells,including optimal removal of tumor nodules in CRS group,and maximal removal of tumor nodules and heperthermic chemoperfusion in the CRS + HIPEC group with docetaxel (10 mg/rabbit ) and carboplatin (40 mg/rabbit) at 42 ℃ for 30 min.The primary endpoint was overall survival.The secondary endpoints were body weight,biochemistry,major organ functions and serious adverse events.Results The success rates of rabbit PC model were 100% (42/42).The clinicopathological feature of the model was similar to peritoneal carcinomatosis in human.Overall survival was 18-30 days ( median 24 days) in control group,20-40 days ( median 27 days) in CRS group,and 23-55 days ( median 46 days) in CRS plus HIPEC group ( CRS alone group VS control group,P ＞ 0.05;CRS + HIPEC group vs pure CRS group,P ＜ 0.01 ).As compared with CRS only or control groups,HIPEC could extend the overall survival by at least 70%.At the baseline,on the day of surgery and 7 days after surgery,the count of peripheral blood cells,liver and renal functions,and biochemistry parameters were all comparable.Serious adverse events occurred in 0 animal in control group,2 animals in CRS group including 1 animal died of anesthesia overdose and another 1died of postoperative hemorrhage,and 3 animals in CRS + HIPEC group including 1 animal died of anesthesia overdose,and 2 died of diarrhea 23 and 27 days after operation.Conclusion For rabbit model of gastric cancer PC,CRS alone could not bring benefit while CPS + HIPEC with docetaxel and cisplatin could significantly prolong the survival with a acceptable safety. Key words: Gastric carcinoma; Peritoneal carcinomatosis; Cytoreductive surgery; Hyperthermic Intraperitoneal chemotherapy