Research - Randomised controlled trial of the effects of fish oil emulsion in total parenteral nutrition upon tumour vascularity in patients with hepatic colorectal metastases
What is the purpose of the study?
The purpose of this trial is to investigate the potential benefits of intravenous feeding supplemented with omega-3 fatty acids, in patients with liver metastases from colorectal cancer (bowel cancer that has spread to the liver). Omega-3 fatty acids are found in fish oils and in preparations like cod liver oil tablets. Intravenous feeding is where a small plastic tube is placed in one of the veins in the arm and the patient is fed directly through this.
What are the possible benefits?
Omega-3 fatty acids are components of the membranes surrounding the cells in the body and are important in controlling production of certain chemicals called cytokines. These cause inflammation (similar to when you bang your arm or get bitten by an insect and it becomes red, warm, painful and swollen). Omega-3 fish oils have been shown to have beneficial anti-inflammatory effects. They have also been shown to have other benefits in patients undergoing surgery, including reducing:• Infection rates• Use for antibiotics• Re-operation• Risk of blood clots in the leg and lung (deep vein thrombosis DVT and pulmonary embolism).
They have also been shown to reduce stay in hospital after operation by up to 7 days and to reduce the death rate following major surgery.
In addition, omega-3 fatty acids may have beneficial effects against cancer cells, in laboratory experiments, omega-3 has been shown to:
• Inhibit cancer cell growth
• Increase cancer cell death
• May make the cancer more responsive to treatment with chemotherapy. However, these results have not been confirmed in humans.
What is involved?
Every patient with liver metastases from bowel cancer in whom an operation would potentially remove all of the liver cancer undergo a laparoscopy (keyhole operation) to directly look at the liver, combined with an ultrasound scan, to further assess whether it will be possible to remove all of the cancer. This is done under a general anaesthetic (i.e. whilst put to sleep). In those patients who are operable, we often keep them in hospital for intravenous feeding prior to the operation to remove the liver cancer.
In this trial participants will be fed intravenously for 3 days with a feeding mixture supplemented with omega-3 fish oils. Prior to starting the trial patients will be carefully examined by a member of the surgical team and have blood samples taken to ensure that there is no risk to them in entering the trial. Assuming everything is fine, they will then have a special magnet scan (MRI scan) of the liver as an outpatient. Within 2 weeks of this, they will be admitted to a surgical ward at the Leicester General Hospital for the laparoscopy. The feeding tube will be inserted on admission and the 3 days of intravenous feeding started. A second magnet scan will be performed immediately prior to starting feeding. In order that there is no error in the results, patients will only be able to drink clear fluids during this time and not to eat anything.
This trial is a 'randomised' trial. In order to identify the effects of the fish oils, we need to compare the feeding mixture with the fish oil added against the feeding mixture alone. Prior to commencing feeding, patients will be randomly selected to receive either the fish oil feeding mixture, or the mixture without the fish oil. In order to eliminate any bias in the results, the patients will not know which mixture they received. A separate record will be kept recording this. At no point in time will the trial influence the best possible care for the patient or their condition.
During the 3 days of feeding, the laparoscopy will be performed. In addition, daily blood tests will be taken to monitor for any adverse effects of the intravenous feeding (this is normal care for any patient undergoing intravenous feeding). After the 3 days of intravenous feeding, a third magnet scan (MRI scan) will be performed to assess the effect on the cancer in the liver.
All patients will then proceed to an operation to try to remove the liver cancer within the next week. The removed cancer will be analysed by a pathologist under a microscope to check that all of it was successfully removed (this is normal practice in the removal of any cancer). At the same time, the pathologist will also assess the vasculature (amount of blood vessels) in the cancer to see if the fish oil has had any effect on them. After this, a small amount of the removed cancer will be used to measure the omega-3 concentration in the cancer.
Routine clinical care will persist after the operation, and the patients will be followed up as usual in the outpatient clinic.
Are there any side effects?
There are very few side effects of the treatment in this trial. Omega-3 fatty acids have been shown to be a safe nutritional supplement, which is why preparations like cod liver oil are available in the supermarket. The small risks in this trial are potential allergy to omega-3 fatty acids. It also can have effects on other salt and sugar levels in the blood, which is why daily blood tests are taken and monitored and it is important to monitor the fat levels in the blood to ensure that they do not rise to high, as this may affect some of the organs in the body including the liver. Other side effects include nausea and reduced appetite. All of these side effects are very uncommon.
What are the possible disadvantages and risks of taking part?
The potential risks of this trial are virtually identical to those that would occur should you not participate in this trial, aside from the potential side effects of omega-3 listed above, which are very uncommon. MRI scanning has very small risks including allergic reaction to the contrast agent and claustrophobia (the scanner is quite small and this may make some people anxious). The insertion of the tube for feeding into the veins also has some small risks including infection and bleeding.
This clinical trial will not adversely affect the care of any patient entering the trial. The same safeguards are in place as would be in routine clinical care. All data collected will be kept completely confidential. The results of the study will be fed back to the participants. Should the treatment be beneficial, the results may be shown to other patients with the same condition and treatment be offered to them. The results may also be reported in medical journal and at conference presentations to educate other medical professions. All information will be strictly confidential.
The study is being organised and funded by the Department of Surgery at the Leicester General Hospital with help from Bbraun, who are a pharmaceutical company.
