I Medical Hypotheses Medical Hypotheses (1995), 44, 149-154 © Pearson Professional Ltd (1995) Adjuvant Therapy with Essential Fatty Acids (EFAs) for Primary Liver Tumors: Some Hypotheses G. F. BARONZIO*, L. SOLBIATIt, T. IERACEt, F. BARZAGHIt, F. SUTERt, M. AIROLDIt, G. BELLONI*, F. RAVAGNANI**, P. NOTTI**, A. GRAMAGLIA**, F. GALANTE*, T. LIVRAGHI$ * Association 'P Merlo', Via Volta 40, 20029 Turbigo (Mi), **National Cancer Institute, Milan, t Busto Arsizio Hospital, ~ Vimercate Hospital, Italy (Reprint requests to GFB) Abstract -- Hepatocarcinoma is responsible for approximately 1 million deaths annually. It is usually discovered at an advanced stage and, if inoperable, has a poor prognosis. New therapies combining chemotherapy, hyperthermia, radiotherapy and immunomodulators have been recently attempted with various levels of success. Once the tumor is detected at an early stage, some possibilities of cure seem to emerge either by intratumoral percutaneous injection (PEI) of alcohol or by chemoembolization and interstitial hyperthermia. When the tumor volume is more than 5 cm, these therapies are less successful and radiotherapy can be used. All the techniques described have some limits; PEI, for instance, does not achieve a complete eradication of lesions >3 cm and a non-homogenous alcohol distribution within the tumor leads to areas of necrosis. Radiotherapy, even if effective, is limited by dose-related radiation hepatitis. Another important limiting factor is the incomplete response to therapy and tumor recurrence. Essential fatty acids, especially gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) are discussed here for their ability to control primary tumor proliferation and increase response to chemotherapy, radiotherapy and hyperthermic treatment, thanks to their effects on cellular membranes (increased lipoperoxidation and modification of tumor stroma). Introduction For inoperable hepatocarcinomas, various therapeutic approaches have been identified. The so-called inter- stitial therapy's target is to deliver drugs to select damaged tissue preserving surrounding normal tissue (l). Another function of interstitial therapy is the at- tempt to reduce the tumor volume and to lengthen survival. Unfortunately, it has two important limita- tions: 1. the focal nature of the treatment makes this technique unsuitable for diffuse disease or for tumors with dimensions over 5 cm; 2. tumor relapse due to the presence of residual cancer cells at the periphery of the treated lesion. The prognosis depends on tumor histology, its extension and the presence or absence of cirrhosis, ascites and jaundice (2). For unresectable HCC, a palliative treatment could be radiation. Unfortunately, the liver does not toler- ate radiation doses greater than 2500 cGy. Above this dose, injury of normal hepatic parenchyma is the rule. Chemotherapy with doxorubicin seems to be the most active therapy and has obtained a partial re- sponse of 15% (3). All of the therapies described can provide brief palliative benefits; it is therefore urgent to find other drugs or combined therapeutic approaches in order to obtain: a. increased patient Date received 14 September1994 Date accepted26 October 1994 149