Isolated limb infusion (ILI) with anti-cancer drugs is a form of treatment which may be offered to patients with recurrent melanoma or other types of tumour confined to a limb.

A technique which is very similar in principle, but technically much more complex known as isolated limb perfusion (ILP), was developed in the early 1960’s by surgeons in New Orleans, based on early heart / lung bypass technology. In the early 1990’s, the alternative technique of ILI was developed at the Royal Prince Alfred Hospital and is now being performed in a number of other centres in Australia and overseas. ILI is much less complex and requires no surgical incision, yet appears to be just as effective as conventional ILP. Additional benefits of ILI are that it can easily be repeated if necessary, it does not require routine blood transfusion, and can sometimes be performed in patients who would not be considered medically suitable for ILP.

Isolated limb infusion is suited to patients with recurrent melanoma confined to a limb and which cannot be treated by simple surgical means, ILI is thus preferred to other methods of treatment because it avoids the need for amputation, and allows large doses of anti-cancer drugs to be delivered to the limb without affecting the rest of the body. Although there are a number of predictable side effects, complications are rare. As well as avoiding the need for amputation, ILI offers a reasonable chance of long term tumour control and possibly cure, even when there is extensive disease in the affected limb.

Following ILI there is complete disappearance of all visible limb tumour deposits (a complete response) in 40-50% of cases, and good control (a partial response) in another 20-30% of cases.

What is involved in an Isolated Limb Infusion?

The operation involves “isolation” of the affected arm or leg from the rest of the body using a tourniquet which blocks off the normal blood supply to the limb and keeps the anti-cancer drugs confined to it. First, using local anaesthetic and X-ray equipment, small calibre arterial and venous catheters (tubes) are inserted through the skin of the opposite groin by a procedural radiologist. Later that day, in the operating theatre, the actual infusion of anti-cancer drugs is performed (normally after a full general anaesthetic has been given).

Before the anti-cancer drugs are injected into the limb, a totally occlusive tourniquet is placed around the upper part of the limb to prevent leakage into the general circulation of the body. During the ILI procedure, the blood circulating through the limb is warmed by passing it through a heating coil, because the effectiveness of the anti-cancer drugs is increased at raised temperatures. The duration of the ILI procedure (i.e. the period during which the limb is exposed to the anti-cancer drugs) is normally 30 minutes.

When the procedure is completed, the limb is flushed with saline to remove residual drugs, the tourniquet is removed, the arterial and venous catheters are withdrawn, and normal circulation to the limb is restored. The total procedure in the operating theatre usually takes about an hour.

Effects of Isolated Limb Infusion:

The treated limb normally becomes somewhat swollen, warm and pink for several days after an ILI. Sometimes mild “pins and needles” sensations are experienced for the first few days, and very occasionally discomfort in the limb due to inflammation of nerves (neuritis) may persist for a few weeks. The skin may peel a little after a week or two, and growth of nails and hair on the treated limb usually ceases for several weeks. All these are expected results of treatment. They occur because some normal tissues are slightly affected at the same time as the cancer cells are destroyed.

Occasionally more dramatic inflammation of the limb occurs, especially when large doses of anti-cancer drugs and high limb temperatures are deliberately used in cases of disease which has recurred several times or which is particularly extensive. This inflammation usually settles completely in 4-6 weeks. If there is a lot of swelling of the limb in the first few days after an ILI, anti-inflammatory drugs are prescribed and, on rare occasions, a minor operation to release the pressure in the limb may be necessary.

Patients who are particularly sensitive to the anti-cancer drugs sometimes experience mild nausea after the operation, but these symptoms are readily controlled with appropriate medications. A more serious, but very rare side effect, is thrombosis (clotting) in the veins or arteries of the limb. The risk of thrombosis is reduced by administering anti-coagulants (anti-clotting drugs) to the patient and into the limb during the operation, and by taking special precautions during the entire period of hospitalisation. There is nevertheless a risk of limb loss as a result of an ILI, but the chance of this occurring is very small indeed (less than 0.5%) – and it must be remembered that the only other effective treatment option is usually amputation.

Summary:

ILI with anti-cancer drugs is an effective form of treatment for recurrent (secondary) melanoma confined to a limb, and for some other types of tumours. ILI was first performed at the Royal Prince Alfred Hospital in 1992, and over 300 procedures have been performed since then.

WARNING THIS SECTION CONTAINS GRAPHIC CLINICAL IMAGES

Clinical Example of Treatment by Isolated Limb Infusion