Wednesday, January 17, 2001

Cancer therapy stirs lively controversy 'Tumor-tying' likely to be tested despite death of pioneer researcher By Felice Wilson Fate was unkind to Dr. Karel Fortyn. For more than four decades, Fortyn was certain he had a breakthrough cure for cancer. He wanted badly to get it to patients. On Jan. 4, only months after this country's Health Ministry agreed to consider testing his controversial methods on animals -- a necessary step before human therapy -- Fortyn died of a pulmonary blood clot. He was 70. A humble surgeon who made bold claims, Fortyn maintained that his method, known as devitalization, a kind of biological strangulation, could stop most tumor cancers, even in the late stages when malignant cells invade lymph nodes and surrounding tissue. There was no chemotherapy, no radiation. Only blood or bone marrow cancer were exempt from the method, which mainstream surgeons reject because it involves leaving dead tissue in the body, an anathema to conventional surgery. Dead tissue decays and causes infection, or sepsis. Fortyn's procedure, which he had performed on melanoma-infected pigs since 1989 with a 99 percent success rate, is straightforward. Devitalization, or devascularization, involves tying off blood vessels to and from the primary tumor with surgical string and leaving the tumor to die and decompose in the body. Without nourishment from arteries, the tumor dies within days. What happens next is more complex and unclear. In Fortyn's pigs, dead tumors apparently produce an immune response. Unidentified surface proteins create antitoxins that gradually kill off all other tumors, called metastases, throughout the body. Dying cancer cells are replaced with connective tissue. "This method is based on cellular mechanisms and the immune system," Fortyn told The Prague Post weeks before his death. "It is the opposite of radiotherapy and chemotherapy, which kill healthy cells together with tumors. Devitalization does no damage, and patients don't need radiotherapy or chemotherapy after the procedure. "Miracles don't exist," he added, "but we can say that this method works in cases where others fail." Lucky break Fortyn, a 1955 graduate of Charles University medical school, said he discovered devitalization during a routine procedure in 1957. At 27, he operated on a patient and found a tumor-infested stomach. Acting on instinct, and presuming the patient could not be saved, Fortyn tied off half of the stomach and connected the other half to the patient's intestine. "The patient survived and lived for a long time," Fortyn said. "He died of, I think, a heart attack. "This all was just coincidence that became a method," he said. "I didn't know what would happen when I was doing the operation. And I never thought of it beforehand. Afterward, my colleagues did not take it as seriously as I did." Over the years, Fortyn repeated the procedure on 20 patients who were in "a hopeless situation," with tumors in intestines, ovaries or other organs. He claimed "none died of cancer." While continuing his surgical practice in various hospitals, Fortyn used his free time to study the mechanisms of devitalization. His research began in 1971 at the Academy of Sciences' Institute of Animal Physiology and Genetics in Libechov, a central Bohemian town in the Melnik region north of Prague. He got occasional help from institute researchers, who later became his full-time staff. In 1989, the team began testing devitalization on a special breed of pigs with a 57 percent occurrence of hereditary melanoma and a blood type similar to that of humans. They reported a 99 percent success rate. After 24 years, the institute put Fortyn on staff in 1995, and he and his team of seven non-medical scientists devoted themselves fully to the method. The team has published its findings abroad and hosted seminars describing the technique, but because of the concern over dead tissue it attracted almost no takers. Running out of options, they took devitalization to the Czech media about a year ago, demonstrating the procedure and showcasing healthy pigs to journalists. The Health Ministry, urged on by interested government members, finally decided to probe the method. In February, the ministry will make a final decision on clinical testing. Institutes in Switzerland, France and the Republic of Georgia are now expected to begin their own research into devitalization. Fortyn's team also will continue studying the proteins that cause tumor regression, but it is currently focused on finding a new leader. The communist regime certainly didn't help Fortyn's research. It was cumbersome and hard to persuade. Still, he believed the greatest deterrent was the resistance of physicians to leaving a dead tumor in the body. "They are afraid because this is something unheard of," said Fortyn. "This is against what students have been taught at school, that dead tissue must not be left in the human body because it can cause sepsis. It is completely against the spirit of teaching at universities." Fighting criticism Dr. Karel Havlicek, head of the Czech surgery association, is a skeptic. "Leaving a devitalized organ in the human body can put a man's life in danger," he told the daily Pravo. Havlicek opposes testing on human patients, calling it a "gamble." Fortyn said that blood infection cannot occur with devitalization, as both arteries and veins are blocked, not only arteries. "The dead tissue is cut off and killed by a cellular mechanism," he said. Dr. Jan Zaloudek, who is preparing testing protocol at Masaryk Oncological Institute, acknowledges that Fortyn's test piglets show no sign of sepsis, but said his medical team will evaluate toxicity. But he doubts the immunological mechanism thought to kill metastases in the genetically altered pigs will act as effectively in humans. "The immunology of tumors ... is not so simple," said Zaloudek, who has researched cancer vaccines in the United States and now works with Mayo Clinic's Immunology Program. "At best, the method can stabilize some growing tumors in, let me hope, 10 to 20 percent of patients." He doubts metastases in lungs and kidneys will shrink. He said melanoma tumors in the pigs have about 77 percent more anti-cancer lymphocytes than in human melanoma tumors. Zaloudek stressed that the Czech oncological society does not consider devitalization a breakthrough in cancer research and the press should not "describe us as crazy people searching for something that can't be done." Like Zaloudek, Dr. Pavel Klener, chairman of the oncological association, thinks devitalization has a good experimental basis, but awaits clinical test results. "Many methods which proved effective in animals, failed in humans," he said, citing proresid, a mid-1960s drug that killed a variety of gynecological tumors. But while testing is under way, Fortyn's and Zaloudek's teams will continue receiving calls from desperate cancer patients around the globe. "It's terrible to explain to them that we cannot treat them," said Zaloudek."We cannot help people with promises, but with facts. At the moment, facts are insufficient." Killing tumor Cancer researchers today are looking for nontoxic ways to kill or shrink tumors by inhibiting their blood supply. Dr. Judah Folkman, credited with developing two anti-angiogenic drugs -- angiostatin and endostatin -- at Boston's Children's Hospital, describes the leading therapies under experimentation or clinical trial: Anti-angiogenic therapy: Drugs such as endostatin and angiostatin regress or stop the growth of capillaries to the tumor with specific proteins. At least 20 drugs are in clinical trial in about 100 medical centers in the United States. About seven are in the final testing phase. Antivascular therapy: Drugs like Combrestatin cause rapid clotting and some necrosis in the tumor during the first day of administration. Later, it may help block capillary growth. Embolization: Clotting compounds are injected into the arteries feeding a tumor through a catheter. The tumor is removed after a few days. Devitalization: The primary tumor is surgically tied off from its blood supply and left in place, triggering an immune system response that gradually kills other tumors. -- Jana Janovska contributed to this report. Felice Wilson may be reached at fwilson@praguepost.cz