title: Surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for gastric cancer: a systematic review and meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  Adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) is a therapy which combines thermotherapy and intraperitoneal chemotherapy. It is theoretically powerful for patients with advanced gastric cancer (AGC), but is there evident advantage in clinical practice? We need evidence to guide our decision-making.
  
  
  OBJECTIVE
  Meta-analysis was performed to assess the effectiveness and safety of adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for patients with resectable locally advanced gastric cancer, and to provide the reference for clinical practice and study.
  
  
  METHODS
  We searched the Cochrane Library, PubMed, Embase, Web of Science and Chinese databases (Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang) electronically and also retrieved papers from other sources (tracing related references and communication with other authors). All relevant randomised controlled trials (RCTs) were collected to compare surgery combined with IHIC to surgery without IHIC for AGC. There were no language restrictions. After independent quality assessment and data extraction by two reviewers, meta-analysis was conducted by RevMan 5.1 software.
  
  
  RESULTS
  16 RCTs involving 1,906 patients were included. Compared with surgery alone, combination therapy (surgery plus IHIC) was associated with a signiﬁcant improvement in survival rate at 1 year (hazard ratio (HR) = 2.99; 95% confidence interval (CI) = 2.21 to 4.05; p < 0.00001), 2 years (HR = 2.43; 95%CI = 1.81 to 3.26; p < 0.00001), 3 years (HR = 2.63; 95%CI = 2.17 to 3.20; p < 0.00001), 5 years (HR = 2.49; 95%CI = 1.97 to 3.14; p < 0.00001), and 9 years (HR = 2.14; 95%CI = 1.38 to 3.32; p = 0.0007). Compared with surgery alone, combination therapy was associated with a signiﬁcant reduction in recurrence rate at 2 years (RR = 0.42; 95%CI = 0.29 to 0.61; p < 0.00001), 3 years (RR = 0.35; 95%CI = 0.24 to 0.51; p < 0.00001) and 5 years (RR = 0.47; 95%CI = 0.39 to 0.56; p < 0.00001). IHIC was not found to be associated with higher risks of anastomotic leakage, ileus, bowel perforation, myelosuppression, gastrointestinal reaction and hypohepatia, but it increased the incidence of abdominal pain (RR = 21.46; 95%CI = 5.24 to 87.78; p < 0.00001).
  
  
  CONCLUSIONS
  Compared with surgery alone, surgery combined with IHIC can improve survival rate and reduce the recurrence rate, with acceptable safety. However, safety outcomes should be further evaluated by larger samples and high quality studies. Additionally, hyperthermia for the intraperitoneal chemotherapy needs more clinical research.
authors: Evidence-Based Medicine Centre of Lanzhou University, Lanzhou, Gansu Province, China.
authors: Deng-Hai
authors: DH
authors: Mi
authors: Zheng
authors: Z
authors: Li
authors: Ke-Hu
authors: KH
authors: Yang
authors: Nong
authors: N
authors: Cao
authors: Anne
authors: A
authors: Lethaby
authors: Jin-Hui
authors: JH
authors: Tian
authors: Nancy
authors: N
authors: Santesso
authors: Bin
authors: B
authors: Ma
authors: Yao-Long
authors: YL
authors: Chen
authors: Ya-Li
authors: YL
authors: Liu
mesh_terms: D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy / Q000009:adverse effects; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007263:Infusions, Parenteral; D007430:Intraoperative Care; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016019:Survival Analysis