The Effect of Fish Oils on Human Hepatic Colorectal Metastases

Randomised Controlled Trial of the Effects of Fish Oil Emulsion in Total Parenteral Nutrition Upon Tumour Vascularity in Patients With Hepatic Colorectal Metastases

The purpose of this study is to determine whether fish oils - a known source of omega-3 given intravenously (via a 'drip') will help cure secondary deposits in the liver from bowel cancer.

Fish oils have many proven benefits for a wide range of clinical arenas such as ischaemic heart disease, rheumatoid arthritis and inflammatory bowel disease.

Recent research has described the beneficial effects of intravenous fish oils for surgical patients, such as reduced hospital stay, reduced re-operation rate and reduced requirements for intravenous antibiotics. These are in part due to the anti-inflammatory effects of fish oils.

There is evidence that fish oils are also effective against cancer, large population studies indicate that diets rich in omega-3 are associated with a lower incidence of cancer, and in vitro and animal studies demonstrate anti-tumour effects of fish oils

1. Fish oils inhibit the growth of different human cancer cell lines
2. They act specifically on tumour cells only and do not impair the function of normal cells
3. EPA and DHA inhibit the growth of human cancer cell lines and enhance apoptosis.
4. Fish oil induces apoptosis in human colorectal cancer cell lines in-vitro after 48hrs incubation
5. Fish oil has been shown to inhibit the proliferation activities, inhibit the invasive activities and increase the apoptosis of human pancreatic carcinoma cell lines in-vitro after only 48hrs of exposure
6. Fish oil has been shown to enhance colorectal adenocarcinoma cell lines sensitivity to radiotherapy
7. Fish oil has also been shown to reduce the incidence of liver metastases in experimentally induced ductal pancreatic cancer in rats after 30 weeks of oral treatment with an omega-3 supplemented diet.
8. Lung cancer xenografts in animals fed with fish oil showed significantly increased tumour regression in response to doxorubicin compared to those fed with omega-3.

This study aims to assess the effect of omega-3 FA upon hepatic colorectal metastases in a pilot study. 20 patients will be selected for this pilot study with potentially resectable hepatic colorectal adenocarcinoma metastases. 10 patients will receive total parenteral nutrition (TPN) without fish oils (controls), 10 will receive fish oil containing lipid emulsion in their TPN.

Changes in tumour angiogenesis (increased angiogenesis is associated with a poorer prognosis in hepatic colorectal metastases) will be investigated using digital contrast enhanced MRI scanning, and markers of angiogenesis will be investigated in blood and resected tumour samples from the patients.

It is a randomised controlled double blind trial.

Inclusion Criteria:

1. Aged 18-80
2. Able to give informed written consent
3. Diagnosis of respectable hepatic colorectal metastases on radiological and laparoscopic appearances

Exclusion Criteria:

1. Patients already taking fish oil supplements
2. Hypersensitivity to fish-, egg-, or soy protein, or to any of the active substances or constituents in the lipid emulsion
3. Hyperlipidaemia
4. Severe blood coagulation disorders
5. Severe renal insufficiency (Creatinine >200)
6. Any general contra-indications to infusion therapy - pulmonary oedema, hyperhydration, decompensated cardiac insufficiency
7. Any unstable medical conditions - uncontrolled diabetes mellitus, acute myocardial infarction, stroke, embolic disease, metabolic acidosis, sepsis, pancreatitis
8. Patients undergoing conventional neo-adjuvant chemotherapy.