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Tumors on ice offer hope for many inoperable patients

by Marilynn Marchione
Knight Ridder News Service

The patient was out cold, surrounded by surgeons, ultrasound technologists, technical consultants and imaging experts, and things were about to get much, much colder.

video screen of sonogram with surgeons watching Seven slender probes had been poked through his skin and precisely positioned throughout his prostate gland. Now all eyes were focused on the grainy, grayish picture of it on the two ultrasound monitors in the surgical suite.

"Start the freeze," the surgeon told a technician, who activated a control for one of the probes. Highly pressurized argon gas shot through the skinny tube, and a teardrop-shaped ice ball formed around its tip, deep inside the prostate tissue.

photo of the 7 probes, their tips covered in ice On the ultrasound monitor, the image of the man's prostate faded to black as the tissue reached a temperature of minus 40 centigrade, or 72 below zero Fahrenheit. The tissue was destroyed, and with it, hopefully, was the cancer.

Cryosurgery -- turning tumors into ice balls via minimally invasive operations -- is growing in popularity and success around the nation for a variety of cancers. It offers hope for many patients whose tumors are inoperable, who are too old or sick for surgery, or whose cancers have recurred after radiation or chemotherapy.

At least 100 hospitals in the United States now offer it; at least one is doing it experimentally for breast cancers in women too old or frail for surgery. Considered experimental just a few years ago, cryosurgery now is covered by Medicare as primary therapy for prostate cancer.

In Madison, doctors at the University of Wisconsin Comprehensive Cancer Center have been using cryosurgery to treat liver and kidney tumors, destroying only the cancerous portion of the organ and preserving function of the rest.

In Milwaukee, Medical College of Wisconsin doctors at Froedtert Memorial Lutheran Hospital have been doing it for liver cancer since 1993, and recently started offering it for kidney and prostate cancers.

For prostate cancer, cryosurgery allows non-surgical destruction of the gland. The prostate is so small -- just slightly larger than a walnut -- that removing just what appears to be the main tumor isn't done because that isn't likely to cure.

"Usually prostate cancer is multifocal. Even though it presents with a predominant cancer in one site, you could have microscopic cancers you cannot see, so you have to destroy the entire gland," explained Fred Lee, a radiologist at Crittenton Hospital in Rochester, Mich., who has performed the most prostate cryosurgeries in the nation -- 840.

A 72-year-old man became the Milwaukee area's first prostate cancer cryosurgery patient at Froedtert in January.

"I didn't have too many other options," said the man, who was diagnosed with cancer in August and had complications from several previous surgeries and procedures for other urological problems. Within two weeks of his cryosurgery, he was getting ready to return to his job as a bank executive.

The gold standard for treating prostate cancer that hasn't spread beyond the prostate to lymph nodes or bone is surgical removal of the gland -- prostatectomy. But not all patients are young or healthy enough to withstand the surgery. Some choose radiation, either external beam or radioactive "seed" implants, but radiation only sometimes cures.

Cryosurgery is an alternative to prostatectomy as well as an option for patients whose cancer recurred after radiation.

"This holds great promise. Here's a whole new group of patients" who now have a new option, said Robert Donnell, co-director of the prostate center at Froedtert and the medical college.

An example is South African Archbishop Desmond Tutu, who had cryosurgery in November 1999 at Emory University Hospital in Atlanta for prostate cancer that had been diagnosed in 1997 and recurred after treatment.

Using extreme cold to treat cancer dates to the 1840s, when an English doctor used iced saline through tubes to treat tumors, Joseph Schmidt, chief of urology at the University of California's San Diego Medical Center, wrote in a review article on cryosurgery published in CA Cancer, a journal of the American Cancer Society, in 1998.

Liquid nitrogen came into use after World War II for skin problems, brain tumors and some neuromuscular disorders, he wrote. The first human prostate cryosurgery occurred in 1966, when it was used to treat urinary obstruction from cancer and an enlarged prostate. But early attempts to use it for prostate cancer were burdened by high rates of a complication called fistula, an opening or tunnel that forms between the rectum and urethra.

The breakthrough came in 1996, when newer equipment came out that allowed the simultaneous use of as many as eight probes that were individually activated and temperature-monitored so doctors could more precisely control what areas were frozen and what tissue was spared. This has made fistulas much rarer, and the use of a warming tube in the urethra to keep it from being frozen along with the surrounding prostate tissue has cut urinary incontinence rates to around 4 percent.

"Newer technology has tremendously lowered the side effects," said Donnell, the Froedtert urologist who did the first prostate cryosurgery in Milwaukee.

But one side effect -- impotence -- is nearly universal. When tumor cells escape, it's often through the neurovascular bundle that controls erections, which is destroyed by cryosurgery.

"If they're not impotent, you haven't done it right and you need to go back and do it again," Donnell said.

About two-thirds of patients who have standard surgical removal of the prostate also develop impotence, according to published studies. Cryosurgery patients can use a vacuum pump device, surgical implants or a drug injected at the base of the penis to produce an erection, Donnell said.

The new cryosurgery technology has improved survival. At an international radiology meeting in 1998, Lee's group presented five-year follow-up results from nearly 600 patients showing disease-free survival, established by biopsies, of 79 percent. More recent patients should fare even better, because the new technology better destroys the entire gland, Lee said.

Dennis Peterson, a sales rep with Endocare Inc., a medical equipment firm based in Irvine, Calif., said more than 100 hospitals around the country are using the company's cryosurgery system, including Froedtert, UW-Madison and Lee's hospital in Michigan. One competing firm makes a system that uses liquid nitrogen instead of argon gas, and a third company recently started marketing a new cryosurgery system that uses pressurized gas like Endocare's.

Cryosurgery requires a one- or two-day hospital stay -- Lee predicts it soon will become an outpatient procedure -- and patients return to normal activities in about a week.

Like prostatectomy, cryosurgery usually is recommended for men who have at least a 10-year life expectancy. That's because prostate cancer is usually so slow-growing that very old men diagnosed with the disease often die of other causes before the cancer is lethal.

The cancer also must be confined to the gland, not spread to lymph nodes or other sites.

"I think its niche is going to be in older gentlemen whose prostate cancer is locally confined who do not want to go through radiation treatment," said Richard Babaian of the M.D. Anderson Cancer Center in Houston.

His group tried cryosurgery for prostate cancer with mixed success in the early 1990s on patients who had failed previous treatment and has been using the newer technology for about a year and a half.

Other cancers increasingly are being treated with cryosurgery as well. At UW-Madison, Lee's son, radiologist Fred Lee Jr., has started using it for kidney cancer. Frank Begun, a urologist at Froedtert, has treated seven patients with it since he began offering it in March.

It's ideal for patients with small tumors on kidneys or who for health or other reasons either don't want or are a poor risk for surgery, Begun said. It also can be used on patients with multiple tumors in both kidneys. The goal is to avoid dialysis and preserve as much kidney function as possible.

"Some of these patients have compromised kidney function to begin with," and can't afford the loss of the entire organ, he said.

The procedure is done laparascopically rather than with a big incision and recovery is much shorter than open surgery.

For liver cancer, cryosurgery is well established. Lee and physician David Mahvi do it at UW-Madison, and surgeon Edward Quebbeman has done about 200 such procedures, starting in 1993, at Froedtert.

"The best candidates are the patients who have tumors of about 4 centimeters or less in areas that would otherwise cause a lot of bleeding or danger to take out," Quebbeman said.

It can be used to treat cancer originating in the liver, as well as cancer that has spread there from the colon or other sites, he said.

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