Cryotherapy for Liver Tumors

Drs. McCarty and Kuhn have brought the readers up-to-date on a new technology--cryosurgery--that is available to treat malignant and benign tumors in the liver. The authors are cautiously optimistic regarding the ultimate success of this therapy. They present the current data, which were generated in patient groups that are the most difficult to treat--those with "unresectable" disease.

The development of the technique and its application to solid organ therapy are nicely explained. Especially valuable is the basic science section that enables the reader to appreciate the actions of deep-freezing at the cellular and microvascular level. Many liver tumors have an increased blood supply, presumably due to tumor-reduced angiogenesis. The specific ability of cryosurgery to create microvascular infarctions may serve as the basis for enhanced cytocidal effects of cold injury.

Evolution of Surgery in Liver Cancer

The surgical treatment of primary and metastatic disease of the liver has evolved via a series of technical developments. Initially, the hepatic arterial, portal, and venous anatomy was mapped in detail, based on the segmental and lobar orientation of its parenchyma. Intraoperative techniques to divide the hepatic parenchyma (clamp crush, finger fracture) followed, as did use of such devices as the ultrasonic tissue fragmenter.

Morbidity and mortality had a great impact on the risk-benefit ratio and discouraged physician and patient acceptance of these operative approaches. High blood loss, which marked the early surgical interventions, significantly limited the opportunity for curative resection. Attention to vascular isolation markedly reduced the amount of blood loss during the resections and in the perioperative period. Methods used to limit blood loss included: specific/segmental inflow control; intermittent use of the Pringle maneuver; early control and division of hepatic venous drainage; preemptive reductions in the central venous and inferior vena caval pressures; and, in selected instances, total vascular (inflow and outflow) exclusion.

The technical feasibility and relative oncologic success of the "swiss cheese" resections that were popularized by John Minton proved that, although the curative results decreased in proportion to the number of metastases, there still remained a finite number of patients who could be cured with surgical resection. The last hurdle was the preservation of adequate liver tissue in patients with extensive disease or preoperative borderline liver function. This preservation of functioning hepatic parenchyma is one of the main advantages of cryoablation and has expanded its surgical utility.

Standard Technique vs Cryosurgery

As an example of the clinical utility of cryoablation, let us consider the patient with early cirrhotic changes and a solitary lesion within the hepatic parenchyma of the right lobe. Standard surgical technique would require complete resection of the right lobe to achieve negative macroscopic margins. Unless the particular patient has a markedly hypertrophied left lobe, it is unlikely that the resulting volume of liver tissue would be adequate to support the patient.

In this setting, controlled, image-guided cryoablation can result in destruction of a minimum number of hepatocytes and enable the surgeon to perform the operative procedure. Thus, a poorly located and therefore unresectable lesion is converted to one that is curable despite the underlying hepatic dysfunction. It is also probable that the procedure can be performed with minimum blood loss and without any inflow control that may increase hepatic ischemia and jeopardize hepatic function.

From a physiologic perspective, hepatic cryoablation has opened up a new area of investigation. In the perioperative period, there are a number of poorly understood, yet consistent, physiologic changes such as a reduction in the number of platelets, the presence of myoglobin in the urine, a mild coagulopathy, and an elevation of hepatic parenchymal enzymes. The changes in coagulation status and platelet count are rarely of any clinical significance. However, the excretion of cellular breakdown products, defined in clinical terms as myoglobinuria must be carefully monitored.

Drs. McCarty and Kuhn emphasize the importance of inducing a vigorous diuresis intraoperatively utilizing mannitol, alkalinizing fluids, and increased volume and continuing this procedure in the postoperative period. In our practice, urine is measured for pH and hemoglobin (a surrogate marker for myoglobin, as the urinary dipstick analysis cross-reacts), and urine output is maintained with high-volume, alkalinized intravenous fluids and renal dose(3µg/kg/min) dopamine infusion until hemoglobin is no longer measurable.

A small dilemma is created, however, by the patient in whom a combined resection and cryoablation is to be performed. Volume status (central venous pressure) and urine output are increased to the maximum for cryoablation and minimized for resection to reduce venous pressure. Our approach is to complete the resection, obtain hemostasis, and then proceed with the hydration phase prior to cryoablation. Using this strategy, we have avoided the renal failure associated with excretion of the by-products of tissue destruction in the post-cryoablation period and minimize blood loss during resection.

Refinements for Future Applications

The future of cryosurgery will likely parallel the recent modifications in surgical techniques that rely on less invasive, more percutaneous strategies. New probe designs will allow for variable shielding of the "business" end of the probe so that ablative precision can be improved and intervening structures protected. Modification of the probe to permit maintenance or control of the ice ball size would be a welcome addition.

Imaging techniques that allow three-dimensional analysis during freezing from a single perspective--similar to those used in neurosurgery--would boost the confidence and adequacy of cryoablation. Improved ultrasound devices, miniaturized or able to be fixed to the hepatic surface, would markedly enhance real-time feedback during freezing. Finally, as with all new technology that has a significant, positive early response, a large-scale clinical trial to examine the efficacy cryosurgery in an unbiased environment must be performed.