The End of Cryotherapy for the Treatment of Nonresectable Hepatic Tumors?

Abstract

Liver resection is generally accepted as the standard of care for patients with hepatic metastases from colorectal tumors in the absence of extrahepatic disease and for selected patients with primary hepatocellular carcinoma. However, in any given cohort of patients with hepatic tumors, most will be unsuitable for resection because of the extent of hepatic tumor burden, extrahepatic disease, or comorbidity. Treatment options in this setting include systemic modalities such as chemotherapy, regional interventions such as intra-arterial chemotherapy, and direct tumor ablation. Direct ablative treatments include intratumoral ethanol, laser, cryotherapy, and, more recently, radiofrequency ablation. Until the advent of radiofrequency, direct intratumoral ethanol and cryotherapy were perhaps the most widely used ablative approaches. Ethanol can be injected percutaneously and does not rely on costly equipment for delivery, and treatments can be repeated. Cryotherapy uses liquid nitrogen at )196 C delivered through a closed triplelumen probe and relies on cooling of liver tumors to at least )35 C. Tumor cell death occurs as a consequence of the formation of intracellular crystals during rapid freezing. Although widely used over the past decade, cryotherapy for liver tumors is not without problems. Freezing can lead to cracking or shearing of the liver parenchyma, andmajor hemorrhage results if these shearing injuries extend into major vessels. Late hemorrhage and intrahepatic abscesses related to biliary injury are also recognized complications. In addition to these local effects of cryotherapy, there are systemic side effects: the cytokine-mediated systemic illness associated with cryotherapy is characterized by fever, tachycardia, and tachypnea. This is known as the cryoshock syndrome and, in particular, can be associated with pleural effusion, diffuse lung injury, and acute renal tubular necrosis. The role of cryotherapy has become increasingly challenged since the advent of radiofrequency thermal ablation. This technique involves the passage of alternating high-frequency current (typically 10 kHz) through tissue. The molecular agitation caused by high-frequency energy leads to an increase in temperature in the tissue through which the current passes without causing muscle contraction or pain. If the field is applied between two equal-sized electrodes, the current flow per unit area of the electrode (current density) is similar in both electrodes. However, if one electrode is smaller, then, because the same total amount of current still has to flow, the current density is much higher at the smaller electrode, with a correspondingly higher temperature. Commercial availability of cooled-tip multiprobe electrodes equipped with probe-tip thermal sensors now permits the creation of a precise hepatic parenchymal ablation. In an important study, Scudamore et al. performed radiofrequency ablation of resectable liver tumors in 10 patients (7 patients with colorectal liver metastases) and then undertook liver resection in 9 of these individuals within 6 weeks of the ablation. On histological examination of the resected specimen by using nicotinamide adenine dinucleotide (NADH; a histochemical technique for demonstration of tissue oxidative enzyme activity), ablated tissue was recognized in all nine cases. The Received October 15, 2004; accepted December 2, 2004; published online March 3, 2005. Address correspondence and reprint requests to: Ajith K. Siriwardena, MD, FRCS; E-mail: ajith.siriwardena@cmmc.nhs.uk.