title: The effect of perfusate buffering on toxicity and response in isolated hepatic perfusion for uveal melanoma liver metastases.
abstract: BACKGROUND
  Isolated hepatic perfusion (IHP) is a treatment option for patients with liver metastases. Previous studies have found that liver toxicity is one of the limiting factors, and in an attempt to reduce the toxicity a buffering agent was added to the perfusate. The aim was to retrospectively analyse if this buffering reduced toxicity and complication rates.
  
  
  METHODS
  A retrospective review of 52 consecutive patients with uveal melanoma liver metastases treated with IHP between 2005 and 2013. Patients were followed by daily liver function tests (LFT). Toxicity was graded according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE; United States Department of Health & Human Services, Washington, D.C), complications according to Clavien-Dindo and response according to RECIST-criteria.
  
  
  RESULTS
  Thirty-six patients were treated with a buffered perfusate and 16 patients without buffer. There was no difference in age, gender, largest tumour size or number of tumours between the groups. There was a significantly lower mean in peak ALT, AST, PK (INR) and bilirubin when comparing buffer with no-buffer. There were five major complications without a significant difference between the groups (8.3 vs. 12.5%, p = 0.33). There was a lower complete response (CR) rate (11 vs. 44%, p = 0.023) and a trend for shorter time to local progression (9.2 vs. 17.6 months, p = 0.096); however, not significant in multivariate analysis. There was no difference in survival (24.2 vs. 26.0 months, p = 0.43) between the two groups.
  
  
  CONCLUSIONS
  Adding buffer to the perfusate during IHP significantly reduces postoperative LFTs; however, without a reduced complication rate. Interestingly, buffering also seems to reduce the response rate; however, this did not translate into a survival difference. To address if buffering adds any clinical benefit to the patients concerning toxicity, a larger prospective trial is necessary.
authors.affiliation: a Department of Surgery, Institute of Clinical Sciences , Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital , Gothenburg , Sweden.
authors.forename: Ilan
authors.initials: I
authors.lastname: Ben-Shabat
authors.affiliation: a Department of Surgery, Institute of Clinical Sciences , Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital , Gothenburg , Sweden.
authors.forename: Valerio
authors.initials: V
authors.lastname: Belgrano
authors.affiliation: b Department of Thoracic Surgery, Institute of Clinical Sciences , Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital , Gothenburg , Sweden.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Hansson
authors.affiliation: a Department of Surgery, Institute of Clinical Sciences , Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital , Gothenburg , Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Olofsson Bagge
keywords: Malignant melanoma; isolated hepatic perfusion; melphalan; toxicity