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The effect of perfusate buffering on toxicity and response in isolated hepatic perfusion for uveal melanoma liver metastases

Journal article
Authors Ilan Ben-Shabat
Valerio Belgrano
Christoffer Hansson
Roger Olofsson Bagge
Published in International Journal of Hyperthermia
Volume 33
Issue 4
Pages 483-488
ISSN 0265-6736
Publication year 2017
Published at Institute of Clinical Sciences, Department of Surgery
Pages 483-488
Language en
Links 10.1080/02656736.2017.1286046
Keywords Malignant melanoma, isolated hepatic perfusion, toxicity, melphalan, isolated limb perfusion, term-follow-up, malignant-melanoma, choroidal, melanoma, phase-i, melphalan, experience, survival, cancer
Subject categories Cancer and Oncology, Surgery


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.

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