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Lugaresi et al. Hepatoma Res 2018;4:67 Hepatoma Research
DOI: 10.20517/2394-5079.2018.88

Original Article Open Access

Endolymphatic immunotherapy for advanced
hepatocellular carcinoma: an update of our
experience

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Marialuisa Lugaresi , Yuval Katz , Riccardo Bertelli , Noa Ruhrman , Lorenza Puviani , Giuseppe
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Cavallari , Caterina De Vinci , Giancarlo Pizza , Bruno Nardo 1
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1 Department of Experimental, Diagnostics and Medicine Specialty, S. Orsola-Malpighi Hospital, University of Bologna, Bologna 40138,
Italy.
2 Module of Immunotherapy, S. Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy.
Correspondence to: Dr. Marialuisa Lugaresi, Department of Experimental, Diagnostics and Medicine Specialty, S. Orsola-Malpighi
Hospital, University of Bologna, Bologna 40138, Italy. E-mail: marialuisa.lugaresi2@unibo.it
How to cite this article: Lugaresi M, Katz Y, Bertelli R, Ruhrman N, Puviani L, Cavallari G, De Vinci C, Pizza G, Nardo B. Endolymphatic
immunotherapy for advanced hepatocellular carcinoma: an update of our experience. Hepatoma Res 2018;4:67.
http://dx.doi.org/10.20517/2394-5079.2018.88

Received: 9 Jul 2018 First Decision: 20 Aug 2018 Revised: 25 Sep 2018 Accepted: 26 Sep 2018 Published: 18 Oct 2018
Science Editor: Guang-Wen Cao Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

Abstract
Aim: We report an update of our experience on endolymphatic immunotherapy in patients with advanced
hepatocellular carcinoma (HCC) not eligible for surgery.

Methods: From 2003 to 2009 we enrolled 39 patients with advanced HCC not suitable for surgery. Patients
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underwent monthly endolymphatic injections of 1.5 × 10 -3.0 × 10 IL-2-activated peripheral autologous
lymphocytes and 250U of IL-2. Blood biochemistry every 3 months and imaging studies every 6 months were
performed. Evaluation of the results was done according to clinical and pathological characters mainly including
etiology, Child-Pugh class, size and number of lesions, α-fetoprotein, lymphadenopathy, vascular invasion,
Response Evaluation Criteria in Solid Tumours criteria for tumour burden, biochemical parameters and survival
rates.

Results: Ten patients completed 12 therapy cycles, 6 received 6 infusions, 10 only 3-4 injection and 13 patients
received less than 3 injections and where considered not suitable for evaluation. No clinically significant adverse
reactions occurred. Imaging studies showed no significant decrease in tumour mass. Survival of treated patients
was significantly higher with respect to control group (P < 0.0001). The 1-year survival was 0% in the control
group vs. 50% in the treated group. In addition survival of patients who completed 12 therapy cycles appeared
higher with respect to patients who underwent less than 6 cycles without reaching statistical significance due to

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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