Isolated limb infusion (ILI) and perfusion (ILP)

Indications

• Local MDT In-transit melanoma metastases of the limb — multiple recurrent cutaneous / subcutaneous deposits between the primary site and the regional nodal basin where surgical excision is no longer feasible.
• Locally advanced limb melanoma not amenable to wide local excision.
• Cutaneous Kaposi sarcoma of the limb with locally advanced disease (rare / anecdotal; not an established standard indication).
• Merkel cell carcinoma of the limb with multifocal locoregional disease (rare; specialist decision).
• Locally advanced limb soft-tissue sarcoma where limb-sparing surgery is not initially feasible — often combined with TNF-α (limb salvage).
• Symptomatic palliation of bulky, bleeding or fungating cutaneous limb disease.

Contraindications

• Distant visceral or nodal metastases above the perfusion level (relative; sometimes palliative ILI is considered).
• Significant peripheral vascular disease.
• Active arterial / venous thrombosis in the target limb.
• Symptomatic cardiac failure (precludes TNF-α).
• Severe peripheral neuropathy.
• Pregnancy.

Technique

Isolated limb perfusion (ILP)

1. General anaesthesia.
2. Surgical exposure of the femoral / iliac (lower limb) or axillary / subclavian (upper limb) artery and vein.
3. Cannulation of the vessels; connection to an extracorporeal pump-oxygenator circuit.
4. Tourniquet at the root of the limb to isolate the circulation.
5. Hyperthermia (38–40 °C) maintained for the duration.
6. Melphalan 10–13 mg/L of limb volume (or 6–8 mg/L for upper limb) infused, optionally with TNF-α 1–4 mg.
7. Circulation maintained for 60–90 minutes with leak monitoring (radio-labelled albumin).
8. Wash-out of the limb with saline; decannulation and vascular repair.

Isolated limb infusion (ILI)

1. General anaesthesia.
2. Percutaneous placement of arterial and venous catheters into the target limb (via the contralateral femoral approach for lower limb; brachial / cephalic for upper limb) under fluoroscopic guidance.
3. Pneumatic tourniquet inflated to isolate the limb circulation under hypoxic conditions.
4. Melphalan 5–10 mg/L of limb volume + actinomycin D 50–100 µg/L injected into the arterial catheter.
5. Manual recirculation via the catheter system for 20–30 minutes; limb temperature passively rises to 37–38 °C.
6. Wash-out with saline; tourniquet released, catheters removed.

ILI is less invasive than ILP, requires no vascular dissection, has lower acute morbidity, can be repeated more readily, and has comparable efficacy in melanoma in-transit disease in published series. ILP remains preferred in advanced limb sarcoma (where TNF-α is needed) and in some centres for very bulky melanoma disease.

Drugs used

• Melphalan — the standard cytotoxic; alkylating agent. Dose calculated by limb volume (water displacement at induction).
• Actinomycin D — added in ILI in some centres; increases response rates.
• TNF-α (recombinant tasonermin) — in ILP for limb sarcoma; produces vascular collapse of tumour neovasculature. Restricted to centres licensed for its use.
• Cisplatin, dactinomycin and other agents have been used historically; melphalan dominates UK practice.

Outcomes

• Trial ILP for melanoma in-transit: complete response 50–65%; overall response 80–90% in published series (Vrouenraets, Grunhagen).
• Trial ILI for melanoma in-transit: complete response 35–45%; overall response 65–80% (Kroon 2008, Sydney Melanoma Unit data).
• Limb salvage rate for advanced sarcoma (ILP + TNF-α): 70–85% at 5 years in selected series.
• Duration of response is variable; repeat treatment is feasible (especially for ILI).
• Locoregional disease control does not translate into clear systemic survival benefit in melanoma; locoregional therapy is selected for symptomatic / functional benefit and limb preservation.

Adverse events & Wieberdink grading

Acute limb toxicity is graded using the Wieberdink scale:

• Most patients have grade II–III toxicity; grade IV in ~5%; grade V (amputation) rare (< 1% in modern series).
• Compartment syndrome: monitor compartment pressures clinically; fasciotomy if needed.
• Skin desquamation, blistering, hyperpigmentation, transient sensory neuropathy.
• Lymphoedema (chronic).
• Systemic toxicity is uncommon if leak rate < 10% (monitored intra-operatively): nausea, transient marrow suppression.
• TNF-α (if used): hypotension, septic-shock-like syndrome — ICU monitoring; vasopressors at hand.

Practical considerations

• Specialist-centre procedure in the UK. Centres with established programmes include the Royal Marsden Hospital, The Christie, Oxford University Hospitals and several regional sarcoma units; check local Cancer Alliance pathway for current referral routes.
• Pre-operative imaging: limb MRI / CT and staging CT to exclude distant disease.
• Pre-operative vascular assessment (arterial Doppler / CT angiography) for ILP.
• Discussion at melanoma or sarcoma MDT before listing.
• Post-procedure: limb elevation, analgesia, regular Wieberdink assessment, wound and compartment monitoring; physiotherapy for early mobilisation when safe.
• Locoregional therapy is often complementary to systemic therapy in modern melanoma practice — sequencing with immunotherapy and / or T-VEC is a local MDT decision.