Cancer in the liver whether primary hepatocellular carcinoma or metastases from other sites is notoriously difficult to treat and a major cause of suffering and death. Surgery is frequently impracticable and chemotherapy ineffective.
Research has focused on treating these tumors percutaneously, introducing a needle through the skin to kill cancer cells by any means available alcohol, microwave radiation, or laser fibers; or with cryosurgery, using liquid nitrogen to freeze the tumor. The goal is to eradicate cancer in some patients and to palliate symptoms in others.
Since the mid-1990s, researchers have adapted a familiar surgical technique, electrocauterization, to `cook' and destroy liver tumors with heat. This new use was suggested by the use of radiofrequency (RF) electrocautery machines to selectively destroy both animal brain tissue in neurobiology research and heart tissue in patients to treat cardiac arrhythmias.
RF tumor ablation, which can be done percutaneously or through a laparoscopic or open incision, employs a modified version of these machines, which have also been used by surgeons since the 1920s to stem bleeding. RF energy is passed through a needle electrode with an "array" at the tip resembling a miniature grappling hook, which heats the cancerous tissue to 60 degrees Celsius or more.
Heat then breaks down proteins and fuses membranes, resulting in cell death. Ultrasound is used to guide positioning, and the electrode may be moved around to treat the entire tumor.
Philip D. Schneider, M.D., an oncologist at the University of California, Davis, said his colleague there, radiologist John P. McGahan, M.D., was the first to conceive of treating cancer with RF and to test it in the laboratory.
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Curley's group has treated the largest number of liver cancer patients with RF ablation, destroying as many as seven liver metastases in a single patient. He said the tumor size limit is about 8 centimeters using current technology, but he is developing electrodes to treat larger areas.
RF ablation has other advantages over competing approaches, proponents claim. It has proven safer than cryosurgery, causing less bleeding. Unlike alcohol injection, it does not require multiple painful injections. And it is more powerful than laser ablation.
In a trial in Houston and Naples, Italy, Curley and colleagues have treated about 250 patients with liver tumors. The July 1999 Annals of Surgery will publish a report on the first 123 patients, about 75% of whom were treated during a laparotomy and 25% percutaneously.
Low Recurrence Rate
"In this group of patients, we saw a very low recurrence rate in the treated tumors less than 3%," Curley said. "And more importantly, an extremely low complication rate, also under 3%." Studies of cryoablation have found complication rates ranging from 25% to 60%, he said, including serious problems such as renal failure, liver dysfunction, and severe bleeding.
Patients must be chosen carefully, experts said. Good candidates for curative RF ablation will have had successful eradication of the primary tumor, and no metastases outside the liver. Of this group, Curley said "a significant proportion" might benefit. Given a baseline resectability of about 25% of patients with liver metastases, Schneider estimated that the technique might add another 5% or so.
"In patients with tumors scattered in both lobes, we have resected the tumor in one lobe and radiofrequency-ablated it in the other," preserving liver function in the RF-treated lobe, Curley said. "Those are patients who in the past had no good options." Allan E. Siperstein, M.D., and colleagues at the University of California, San Francisco, reported success in palliative treatment of patients with neuroendocrine metastases in the liver. These metastases cause complications related to excess hormone secretion, which were relieved through RF ablation.
Keeping the Lid on
Schneider said oncology's experience with cryosurgery initial overenthusiasm leading to use in inappropriate situations, and finally disillusionment led investigators working on RF ablation to take a more cautious tack. "It's been approached with some circumspection, I think, because of the bad experiences with cryosurgery," he noted. "The community of people interested in this has done a pretty good job of keeping the lid on." He predicts, however, that the "lid is about to blow off" as a result of intensive marketing by the companies that make the equipment. "I think there are only a few radiologists that are capable of doing this well," he added. "It is inevitable that inappropriate selection and inadequate technical prowess will cut into the early good results."
Curley observed that RF ablation has grown rapidly. "Right now in this country," he said, "there are easily 50 or 60 centers that have started it," though most have treated only a few patients.
The technique has also been tried in prostate cancer, but the results have been less satisfactory, Curley said. A trial at M. D Anderson is testing it as a less invasive way of treating early stage breast cancer. Because RF ablation is untried in that disease, the tumors are surgically removed following RF treatment. But "in every patient we've treated so far, it has completely killed the tumor," Curley said.
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