Minimally Invasive Isolated Limb Perfusion (MI-ILP) for Locally Advanced Melanomas and Sarcomas of the Extremity

Minimally invasive isolated limb perfusion for locally advanced melanomas and sarcomas of the extremity. Melanoma in-transit metastasis will develop in approximately 3-5%of patients with high risk early stage melanoma. They appear as tumor deposits in the dermal or subcutaneous tissue.

The hypothesis is that ITM originates from tumor cell emboli entrapped in dermal lymphatic vessels, but the underlying pathophysiology is not completely understood. Minimally invasive isolated limb perfusion is a treatment option for patients with locally advanced melanomas and sarcomas of the extremity. It is the minimally invasive counterpart of isolated limb perfusion.

The diseased extremity is isolated from the systemic circulation, connected to a heart-lung machine, and then locally perfused with a high dose of chemotherapy. In this video, we treat a patient with extensive melanoma in-transit metastasis in the left leg, initially treated with immunotherapy, but progressing. The leg volume is calculated by the summation of circumferential measurements every 5 centimeter calculating the volume of a cone.

For upper limbs, we give melphalan at a dose of 13 milligram per liter and for lower limbs at a dose of 10 milligram per liter. A scintillation probe is placed above the heart of the patient to be able to detect any leakage of radioactive technetium from the isolated limb to the patient. To calibrate the leakage monitoring system, a small dose of 10 technetium bound to albumin is injected peripherally.

To calculate the biological halftime, the activity is then measured for at least 20 minutes. In the meantime, all interventional radiological tools that are needed to access the femoral artery and vein are prepared on a separate sterile table. One dose of heparin at a dose of 100 units per kilogram body weight is administered systemically.

The superficial femoral vein is localized using ultrasound and punctured with a 12-centimeter 20 gauging geography needle at approximately 15 centimeter below the inguinal ligament. After puncturing the vein, a 0.018-inch introducer guidewire is placed. The needle is removed.

A 10-centimeter long 4 French mini access introducer is placed over the wire. The guidewire and the inner dilator of the introducer are then removed. Vascular access will be confirmed by the aspiration of blood via the introducer, as well as hand injection of a small dose of iodinated contrast medium under fluoroscopy.

A 0.035-inch exchange guidewire is introduced via the 4 French introducer and the position is verified by fluoroscopy. Adequate predilation of the entry tract is performed with several dilators over the exchange wire. After sufficient predation, a 12 to 14 French Bio-Medicus NextGen venous cannula is placed over the exchange wire.

The cannula is secured with an ethilon suture. The venous catheter is flushed with heparin saline. After securing the venous catheter, the superficial femoral artery is identified using ultrasound in a similar way.

The artery is punctured with a 20-gauge angiography needle. After puncturing the artery, a 0.018-inch introducer guidewire is placed. The needle is removed.

A 10 centimeter long, 4 French mini access introducer is placed over the wire. The guidewire and the inner dilator of the introducer are then removed. Vascular access will be confirmed by the aspiration of blood via the introducer, as well as hand injection of a small dose of iodinated contrast medium under fluoroscopy.

A 0.035-inch exchange guidewire is introduced via the 4 French introducer and the position is again verified by fluoroscopy. The introducer is removed after this but the exchange wire is left. Because of the need of large-bore arterial catheters, a pre-close technique facilitated by suture-mediated closure devices is performed before introduction of the cannula.

Over the exchange wire, two Perclose ProGlide closure devices are sequentially introduced into the artery. The preliminary sutures will be placed at the 10 o'clock and the 2 o'clock positions. The placed sutures are not yet being tightened, but the suture limbs are clamped and placed slightly away from the puncture site.

Thereafter, a 10 to 12 French Bio-Medicus NextGen arterial cannular is placed over the guidewire into the superficial femoral artery. Before connecting the limb to the perfusion system, it is confirmed that all air bubbles are out of the tubes. The limb is then isolated with the placement of two Esmarch tourniquets proximal to the site of the catheterization.

Optionally, these can also be placed over the catheters. The clamps are moved from the arterial and venous cannulas to the shunt, and the perfusion is started. Three thermistors for temperature monitoring are inserted, one in the ingoing blood cannula, the second, 15 centimeter subcutaneously above the knee joint, and the third, 15 centimeters subcutaneously below the knee joint.

If there are no tumors in the foot, the foot is wrapped with another Esmarch bandage to minimize postoperative toxicity in the sole of the foot. Finally, a sterile drape is wrapped around the leg to maintain limb temperature and the temperature of the ingoing blood is set to 39 Celsius. When a steady perfusion is established with a flow rate of approximately 501, 000 milliliter per minute, a high dose of 100 technetium is added to the perfusion circuit to detect any leakage from the limb to the systemic circulation.

If no signs of leakage is present, a 10-minute infusion of melphalan at a dose of 10 milligram per liter limb volume for lower limbs and 13 milligram per liter limb volume for upper limbs is started. For patients with inoperable sarcomas or repeat ILP procedures for patients with melanoma TNF-1 to 4 milligram can be administered as a bonus dose 10 to 15 minutes before the melphalan infusion. After the melphalan infusion, the perfusion is continued for an additional 45 minutes with special attention to any potential leakage, blood loss, flow rate, and temperature development in the limb.

After a total perfusion time of 55 minutes with melphalan, the leg is rinsed with three liters of Ringer's acetate and the leg is massaged to help emptying the venous reservoir. The clamps are then moved from the shunt to the arterial and venous cannulas and the Esmarch band is removed and the leg is disconnected from the perfusion system. The arterial flow is re-established first, where the arterial catheter is removed and the limbs of the two Perclose ProGlide sutures are pulled and tightened.

The snared knot pusher of the Perclose ProGlide system is then used to lock the knot of the sutures. The venous catheter is removed and pressure to the groin is applied for a total of 5 to 10 minutes and no bleeding is confirmed. At the end of the procedure, a normal blood flow to the foot is controlled using a vascular ultrasound.

Steri-Strips are placed at the catheter insertion place. No stitches are needed. After extubation, the patient will be monitored at a postoperative care unit for 4 to 6 hours and then transferred to the general surgical ward.

If you compare isolated limb fusion with minimal invasive isolated limb perfusion, it has the advantage of percutaneous access and therefore avoiding the risks of an open surgical wound. Operation times are shorter and the early response rates are similar compared with an open ILP. In conclusion, minimal invasive isolated limb perfusion is a safe and feasible treatment with the same treatment characteristics as open ILP with the advantage of a minimal invasive vascular access.