title: Cytoreductive surgery and HIPEC for peritoneal metastases combined with curative treatment of colorectal liver metastases: Systematic review of all literature and meta-analysis of observational studies.
abstract: OBJECTIVE
  Assess the overall outcome in colorectal cancer (CRC) patients that present with a combination of peritoneal metastases (PM) and liver metastases (CRLM) after curative resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the current literature.
  
  
  METHODS
  A systematic literature search according to the PRISMA guidelines was conducted using the PubMed database of the U.S. National library of Medicine using the keywords: colorectal cancer, liver metastasis, extra-hepatic, peritoneal metastases, peritoneal carcinomatosis, cytoreductive surgery (CRS), HIPEC and combinations hereof. Papers focussing on CRS and HIPEC for PM combined with curative treatment of CRLM were included, provided sufficient information on survival outcomes could be extracted. Duplicate publications were excluded. Meta-analysis was performed using the method described by Tierney et al.
  
  
  RESULTS
  After screening and full-text assessment of 39 papers, six articles were included containing data on combined PM and CRLM in patients treated with curative resection of both sites and HIPEC or early postoperative intraperitoneal chemotherapy (EPIC). Three articles provided enough statistical information for meta-analysis. Pooled hazard ratio (HR) was extracted from survival curves and was 1.24 (CI 0.96-1.60). A comparison was made with patients presenting with isolated PM undergoing CRS and HIPEC and with patients with disseminated disease undergoing (modern) systemic chemotherapy.
  
  
  CONCLUSIONS
  In the absence of randomized controlled studies, we found in this systematic review and meta-analysis of patients with a combination of colorectal metastases in the liver as well as in the peritoneum show a trend towards a lower overall survival after curative resection and HIPEC, when compared to patients with isolated peritoneal metastases after CRS and HIPEC (pooled HR1.24, CI 0.96-1.60). However, patients with metastatic CRC show a tendency towards increased median overall survival after CRS and HIPEC combined with resection of liver metastases when compared to treatment with modern systemic chemotherapy.
authors.affiliation: Dept. of Surgical Oncology, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. e.decuba@vumc.n
authors.forename: E M V
authors.initials: EM
authors.lastname: de Cuba
authors.forename: R
authors.initials: R
authors.lastname: Kwakman
authors.forename: D L
authors.initials: DL
authors.lastname: Knol
authors.forename: H J
authors.initials: HJ
authors.lastname: Bonjer
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
authors.forename: E A
authors.initials: EA
authors.lastname: Te Velde
mesh_terms: D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007263:Infusions, Parenteral; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D019370:Observation; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy*