Targeted Therapy Combination Overcomes Treatment Resistance In Liver Cancer, Study
Suggests (ScienceDaily - 15/04/2008)
Combo therapy extends life for liver cancer patients: study ( AFP - 8/04/2008)
Study: Liver cancer breakthrough found
Coffee May Curb Liver Cancer Researchers Say Disease Appears To Be Rarer In Coffee Drinkers Than In Non-Drinkers-
(Yahoo News- 2/08/2007)
Nexavar Approved for Liver Cancer-
(Yahoo News- 19/11/2007)
Natural Protein Could Help Spot, Treat Liver Cancer-
(Yahoo News- 19/09/2007)
Scientists say they have discovered how a protein causes liver cancer - it tags cancer preventing cell machinery for destruction. The Japanese and UK team first linked gankyrin to liver or hepatocellular cancer, which affects some 250 million people worldwide, five years ago. Then they discovered that it appeared to encourage DNA synthesis so cells grew unchecked and became cancerous. Now they say, in Cancer Cell, gankyrin promotes cancer by another pathway too. It puts a death mark on cell machinery tasked with deciding which cells in the liver should continue to divide and replicate their DNA and which should die.
For example, if a cell is infected with a virus the protein p53 - sometimes called the "guardian of the genome" - will send out a signal so the cell commits suicide. In hepatocellular cancer, this process is disrupted. Instead, gankyrin binds to an enzyme called mdm2, which gives p53 a molecular label that tags it for death. The marked p53 is then sent to the cell's waste disposer, called the proteasome, where it is broken down and destroyed. This means damaged cells can continue dividing unchecked in the liver and grow into tumours.
Researcher Professor John Mayer, from Nottingham University, said: "It's amazing that gankyrin controls the two major cancer-controlling mechanisms. The cells go on and on dividing and become cancer cells." He said that although around half of all tumours in the body involved p53 defects, gankyrin only appears to be linked to liver cancer, which might be down to certain properties of this organ. "The liver is really interesting because the cells divide very slowly, but the cells can regenerate. They are in a division limbo, so to speak. We think this is why overexpression of gankyrin leads to liver cancer."
Professor Mayer and co-worker Professor Jun Fujita from Kyoto University are now trying to work out the structure of gankyrin in the hope that it will lead to a way to make anti-cancer drugs that block its action. Currently there are few drugs for liver cancer and no cure. Dr Julie Sharp, senior science information officer at Cancer Research UK, said: "Identifying some of the molecular events that may contribute to the development of liver cancer provides an important step towards finding better ways of treating this disease. "This could help improve survival rates in the future."
A two-year study to validate a test to detect early-stage liver cancer has been initiated by the National Cancer Institute (NCI), part of the National Institutes of Health, at six centers across the United States. This test, conceived with the assistance of NCI’s Early Detection Research Network (EDRN), looks at whether a substance called des-gamma carboxyprothrombin (DCP) can identify those at risk for liver cancer.
Validation-proving that the measurement of a substance accurately signifies the risk for or presence of cancer-is the critical step to create a truly useful test. “It’s the first study testing a marker for liver cancer, and the first Phase II EDRN-supported study,” said Sudhir Srivastava, Ph.D., who heads EDRN as chief of the Cancer Biomarkers Research Group in NCI’s Division of Cancer Prevention.
Liver cancer, or hepatocellular carcinoma, with over 20,000 estimated new cases this year in the United States, is both one of the more common cancers worldwide and one of the few cancers in the United States in which the number of new cases is rising, and expected to continue to rise over the next two decades. Frequent surveillance of patients with liver cirrhosis is recommended, but current procedures have shortcomings. Alpha-fetoprotein, a blood test currently used for surveillance of liver cancer, suffers from poor sensitivity and specificity (ability to determine if someone actually has, or does not have, liver cancer). Liver ultrasound is dependent on the skills and knowledge of the technician and can lead to false-negative results. This EDRN-supported study looks to improve upon these negatives.
DCP is a protein precursor of prothrombin, one of the factors produced by the liver to help the blood clot. In patients with liver cancer, this protein seems to be elevated compared to those without liver cancer. Early studies have shown that DCP is better than alpha-fetoprotein for the diagnosis of liver cancer and has close to 90 percent accuracy.
The investigators conducting the validation study, headed by Jorge A. Marrero, M.D., of the University of Michigan, and Paul Wagner, Ph.D., program director in NCI’s Cancer Biomarkers Research Group, plan to enroll 450 patients diagnosed with liver cancer, of which at least 170 will be early stage. Four hundred fifty patients with cirrhosis and no cancer will serve as controls. The participating institutions will collect samples from patients in this study, and the samples will be analyzed for DCP using an assay manufactured by Eisai Company, Teaneck, N.J. The primary goal of the study is to determine whether DCP can lead to improved accuracy in the detection of early-stage hepatocellular carcinoma.
This trial will run for two years and final results are expected in early 2007. If successful, this study will provide a much-needed tool for the early detection of liver cancer. Additionally, EDRN’s gastrointestinal collaborative group is working on two other early novel detection tests for liver cancer for future validation.
EDRN, established by NCI in early 2000, is a broad, interdisciplinary consortium whose work is aimed at both identifying and validating cancer biomarkers for use in early cancer detection, and is divided among collaborative groups studying specific tumors. Numerous proteins and genes have been linked with a variety of cancers, which can make them targets for therapy, as well as targets for identifying the risk of cancer onset, progression, or recurrence.
Cancer Fastest Growing Cancer in U.S. - Report-(Reuters
The Network has currently enrolled approximately 250 patients to date from 6 centers to study demographics, risk factors for liver cancer, liver disease, tumor characteristics and different treatments. The average age of the patients was 59 years and 75 percent are male. Eighty percent Caucasian, 10 percent African American, 4 percent Hispanic and 4 percent East Asian. Most liver cancer patients (87 percent) had underlying liver disease and more than half (52 percent) of those enrolled had hepatitis C infection. A history of alcohol abuse was involved in 20 percent of those cases.
Liver cancer "in the US is almost always associated with chronic liver disease," the Network data show. Survival is "significantly better for those who were asymptomatic at presentation or who were candidates for liver transplantation," Befeler said. The bottom line is that "chemotherapy is generally ineffective for liver cancer. Liver transplantation is the best approach...Most patients also have advanced cirrhosis, so drug metabolism is poor," Befeler added.
Celsion Corporation today announced that the Food and Drug Administration (FDA) will allow the human clinical trial for its investigational therapy for the treatment of liver cancer to proceed. The Phase I study will investigate the use of Celsion's proprietary product, ThermoDox(TM), in combination with Radiofrequency Ablation (RFA). ThermoDox, Celsion's temperature-sensitive liposomal encapsulation of doxorubicin, a common cancer drug, allows focused, concentrated delivery of the drug to the tumor target. The trial will be conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland and will be funded under a Collaborative Research and Development Agreement between Celsion and NIH. Under the agreement, Celsion will supply ThermoDox and provide regulatory and clinical support and NIH will enroll and treat the patients.
The trial is designed to determine the maximum safely tolerated dose and pharmacokinetic profile of ThermoDox when used in combination with RFA in the treatment of liver cancer. The study approach will utilize RFA (80 degrees celsius or above) to ablate (destroy) the center of the tumor and the lower temperature zone (greater than 40 degrees celsius) in the tumor margins to activate and release the doxorubicin to kill any remaining viable cancer cells. Celsion hopes to commence the study before the end of the year. The clinical plans for liver cancer rely, in part, on the preclinical results of the work conducted in large animals by the FDA in conjunction with NIH. These results were presented by Dr. Bradford J. Wood, Senior Clinical Investigator, Diagnostic Radiology Department, Imaging Sciences Program, NIH Clinical Center; Surgery Branch, National Cancer Institute, at the National Institutes of Health at the 89th Annual Radiological Society of North America (RSNA) in December 2003. These results demonstrated that ThermoDox, used in this manner, deposited fifteen times more drug at the tumor site than conventional, intravenous delivery of doxorubicin.
Dr. Augustine Cheung, Celsion's President and Chief Executive Officer said, "Initiating this study is a major step in the evolution of Celsion from a medical device company to a company focused on targeted drug delivery using combination therapies. We believe that the mechanism of action of RFA in conjunction with ThermoDox, using heat-sensitive nanoparticles to target ThermoDox, could result in high deposits of the encapsulated drug, doxorubicin, in the tumor, thus ablating the tumor as well as viable cancer cells in the tumor margin. This may lead to a significant reduction of local tumor recurrence, which is currently the major limitation in using RFA alone to treat liver cancer."
Tony Deasey, Celsion's Chief Operating Officer, added, "Clearance to initiate this study enables us to attempt to address a significant unmet medical need by treating liver cancer. This trial increases our cancer treatment portfolio, building upon our ongoing Phase I trial using ThermoDox to treat prostate cancer in conjunction with Celsion's proprietary microwave heating technology (Prolieve(TM))."
Researchers trying to prevent bone loss in women with cirrhosis of the liver have made an unexpected yet welcome discovery -- that vitamin K may help prevent liver cancer in those most at risk of the disease. The study, which appears in the Journal of the American Medical Association, was originally designed to assess the effects of vitamin K supplementation on bone loss in women with viral cirrhosis of the liver. However, at the end of the study, the researchers realized the women who took the vitamin K had significantly lower rates of liver cancer. "The results suggest a possible role for vitamin K2 in the prevention of liver cancer in women with viral cirrhosis," said study co-author Dr. Susumu Shiomi, a professor of nuclear medicine at the Graduate School of Medicine at Osaka City University in Japan. Shiomi added that "vitamin K2 is cheap and safe to use."
Dr. Jay Brooks, chief of hematology/oncology at Ochsner Clinic Foundation Hospital in New Orleans, explained that people with viral cirrhosis from diseases such as hepatitis C are at an increased risk of developing liver cancer. While researchers still don't know why, Brooks said, "we do know that they run an incredibly increased risk." And, he said, the problem will likely only increase because hepatitis C is being diagnosed in more people.
Between 1996 and 1998, 40 women with viral cirrhosis were recruited for a study in preventing bone loss. The women were randomly assigned to either the treatment group or the placebo group. The treatment group took a pill containing 45 milligrams of vitamin K2 daily. Vitamin K is a fat-soluble vitamin that is produced in the intestines. It can also be found in leafy green vegetables such as broccoli and spinach, vegetable oils, cereals and some meats and cheeses. Excess amounts of this vitamin are stored in the liver. The recommended daily allowance of vitamin K in the United States is 75 micrograms to 90 micrograms (a thousandth of a milligram) per day for women and 75 micrograms to 120 micrograms for men. Most of the women enrolled in the study had hepatitis C. The average age of the study participants was around 60. Two of 21 women in the treatment group developed liver cancer, while nine out of 19 women in the placebo group did. After adjusting for age, severity of disease and treatment, the researchers found the women receiving vitamin K supplementation were nearly 90 percent less likely to develop liver cancer.
The researchers said it wasn't clear how vitamin K could prevent liver cancer, but theorized that it may dampen cancer cell growth. "A number of findings indicate that vitamin K2 may play a role in controlling cell growth. But the mechanisms responsible for the vitamin K-mediated inhibition of cell growth remains unexplained," Shiomi said. "It's an interesting early observation, but it's a very small study," Brooks said. Both the authors of the study and Brooks said these results need to be confirmed with a much larger group of people. And, Brooks added, "it would be extremely premature for anyone with hepatitis C to start taking vitamin K."
He said that in the past there have been studies on vitamins that initially looked promising in the prevention of cancer, but then with further study, were found to be ineffective or, worse, harmful.
A gene that causes liver cancer in mice has been identified by researchers at the University of Illinois at Chicago. When the researchers deleted the gene, called Foxm1b, from liver cells in lab mice, the animals didn't develop tumors. The mice with the deleted gene remained cancer-free even when the researchers tried to use artificial means to induce tumors. "To my knowledge, this is the first time a gene has been directly linked to the growth of cancer cells in live animals," lead investigator Robert Costa, a professor of biochemistry and molecular genetics, said in a prepared statement. The research appeared in a recent issue of Genes and Development. "Foxm1b is expressed in many different kinds of cancer cells, which leads us to believe it plays a key role in promoting the growth of tumors other than liver cancer," Costa added. He and his colleagues have created a prototype for a drug to block Foxm1b activity and starve tumor cells of the protein manufactured by Foxm1b. Depriving tumors of this protein prevents them from multiplying.
Men with diabetes have about a two-fold greater risk of developing liver cancer and other chronic liver diseases compared with nondiabetic men, new research suggests. The same may hold true in women, but the study did not have enough women to reach firm conclusions. "Our study provides evidence that diabetes is an important risk factor for chronic liver disease including (liver cancer)," Dr. Hashem B. El-Serag from the Houston VA Medical Center in Texas told Reuters Health. The study is also the first to show that diabetes precedes, rather than follows, the development of these diseases, he added.
Using the computerized records of the Department of Veterans Affairs, investigators studied all patients with a hospital diagnosis of diabetes between 1985 and 1990. They matched each diabetic patient to three nondiabetic patients and tracked them through 2000. Nearly all of the subjects were men and most had type 2 diabetes. None of the subjects had liver disease when first diagnosed with diabetes. As reported in the medical journal Gastroenterology, the rates of chronic non-alcohol related liver disease and liver cancer were significantly higher in diabetic than in the nondiabetic patients.
The increased risk "seems to be independent of age, gender, ethnicity, or (other) illnesses," El-Serag noted, and is higher in patients with diabetes for 10 years or more. This study, Dr. Adrian M. Di Bisceglie from Saint Louis University School of Medicine points out in an editorial, "provides evidence that long-standing diabetes is followed by the development of liver disease and (liver cancer), suggesting a causative role for diabetes mellitus." The current study supports the team's earlier findings from the same group of patients in which diabetes raised the risk of acute liver failure by 44 percent. In light of the present findings, El-Serag and colleagues recommend regular liver blood tests in diabetic patients. Further studies are needed to examine the association between diabetes and liver disease in women and to clarify the mechanisms behind the link, the authors note
New research supports radiologists who are trying to treat liver cancer by using a "smart bomb" treatment that first shrinks the tumor and then tries to burn it away. The one-two punch extended the lives of patients, claims a German study that appears in the journal, Radiology. The combination therapy also greatly reduces recovery time when compared to the standard surgery treatment, says Dr. Jonathan Susman, an assistant professor of radiology at Columbia University in New York City. Liver cancer remains one of the most deadly cancers, however, and even cutting-edge treatments don't prevent recurrence in many patients with the most advanced forms of the disease. "Traditionally, patients have been plagued by poor survival," says Dr. J.F. Geschwind, director of cardiovascular and interventional radiology at The Johns Hopkins Hospital in Baltimore.
Even after doctors remove the liver tumors through surgery, they return within five years in 75 percent of cases, he says. Liver cancer is especially difficult to treat because it's often the result of existing liver disease, such as cirrhosis or hepatitis. "You can even consider it a side effect," Geschwind says. In other cases, liver cancer develops when tumors migrate from other parts of the body, especially the colon or breast. An estimated 17,300 cases of primary liver cancer -- which do not spread from elsewhere in the body -- are diagnosed in the United States each year, according to the American Cancer Society. Most patients are men. An estimated 14,300 Americans will die of the disease this year.Doctors can try to burn up the tumors with lasers and high-frequency radio waves. However, tumors with diameters of more than 3 or 4 centimeters are often too large to be treated effectively. "You never know how much of the tumor you burned," Geschwind says. "If you leave a little bit of the tumor behind, it returns with a vengeance."
In the new study, the researchers from University Hospital in Frankfurt recruited 162 liver cancer patients whose tumors were large and the result of cancer that had spread from elsewhere in the body. The doctors tried to shrink the tumors and then, if possible, destroy them with lasers. All the patients had a treatment called chemoembolization to shrink the tumors. "We inject the chemotherapy right into the tumor cells, and then cut off the oxygen supply by blocking the blood flow," says Susman, who uses that approach to treat his patients. In the new study, the tumors shrunk in more than half of the patients. Doctors went on to treat their tumors by burning them with lasers. Susman uses a similar approach, utilizing radio-frequency waves instead of lasers. "I treat [the tumor] from the inside first to hamper its defenses and shrink it down, so that I can use a device to burn it away and completely eradicate it. It is the medical equivalent of a smart bomb," he says.
Blocking blood flow to the tumor helps in the burning process, Susman adds. "The blood supply works like the radiator in your car, pulling heat away. When we block the blood supply you no longer have the radiator circulating. You heat the tumor more easily because the heat doesn't go away." The patients who underwent the combination treatment lived for a median of 26.2 months, while the other patients who only received the chemoembolization lived a median of 12.8 months. Those survival rates may seem low, Susman says, but they'd be higher in patients with smaller tumors. Also, the treatment lets patients avoid surgical removal of tumors, which requires months of recovery time and poses great risks, he adds. The German researchers say the dual treatment has applications for lung, bone and lymph node tumors as well.
Researchers from Johns Hopkins University School of Medicine have found that patients with liver cancer treated with a liver transplant are living longer than in past years. They compared transplant results from three eras, 1987-91, 1992-95, and 1996-2001. The study was published online by the Journal of Clinical Oncology in October, and will appear in the December 1 print edition (Vol. 21, No. 23). Worldwide, cancer starting in the liver, called hepatocellular cancer, is a leading cause of cancer-related deaths. The major cause of this cancer is infection with hepatitis viruses. In the United States, where alcoholism is another cause, liver cancer is expected to kill around 14,400 people in 2003.
The only successful treatment for this cancer is surgery. Usually doctors remove the tumor along with part of the liver. But because the liver is damaged, many patients can't withstand losing part of their liver. Beginning in the 1980s, removing the entire liver and replacing it with a transplanted one became another option. The researchers from Johns Hopkins used data from the United Network for Organ Sharing (UNOS), the nation's only organ procurement and transplantation network, to compare survival rates among liver cancer patients who received a liver transplant. In the early years, only about 30% percent of patients were surviving five years. Now, though, around 60% are surviving that long. "These findings are particularly reassuring for patients with tumors that cannot be surgically removed," said senior author Paul M. Thuluvath, MD. More than 80% of liver cancer patients fall into that category, he added.
Thuluvath and his colleagues say that careful selection of patients is the most likely reason transplants for liver cancer have become more successful in recent years. In general, people with small tumors, and no more than three tumors, are offered this treatment. Most treatment centers use this standard, they said, even though it is not an official guideline. Their study couldn't prove that better patient selection was the reason for the improvement in survival, because the UNOS database does not have information about the size of the tumors or how many a patient had. But two other experts, who wrote an editorial accompanying the study, also believe patient selection is a likely cause. Jean-Nicolas Vauthey and Jaffer A. Ajani, of the M.D. Anderson Cancer Center, say survival after transplant could be improved even more if doctors used additional factors like whether the tumor has penetrated blood vessels - to decide which patients should have transplants.
The Johns Hopkins researchers say that liver transplants may be the "optimal treatment" for patients with liver cancer, as long as patients are selected carefully. But this treatment option isn't always readily available to cancer patients. Donor livers, which usually come from people who have died, are a very scarce resource. It can take months for a suitable organ to become available - time that many cancer patients don't have. The Johns Hopkins researchers found that waiting periods for donor livers increased dramatically -- from about one month to seven months or even more than a year -- between 1987 and 2001. To overcome this problem, the Hopkins researchers and the editorialists both suggest trying surgery first on those patients who are eligible. Then, if the cancer comes back, a liver transplant can be performed. Unfortunately, only about 20% of patients have liver cancer that can be treated with surgery. Another option is transplanting liver tissue from a living donor. UNOS data suggest that growing numbers of liver cancer patients are receiving transplants in this way, the researchers write. However, these strategies have not been well-studied, and more research will have to be done to determine their long-term effects on patients with liver cancer.
Italian scientists have treated liver cancer by removing the entire organ, zapping it with radiation, then implanting it back into the body. The surgery is expected to have minimal impact on other organs, which is not the case with traditional radiation therapy. The surgery, performed a year ago on a 48-year-old man with multiple tumors on his liver, appears to be a success, reports the magazine New Scientist. The liver now seems functionally normal and there are no signs of any tumors. Doctors from the San Matteo Hospital in Pavia plan to treat six more patients with the same technique. The physicians say the procedure is still in its infancy and can only be used on the most serious of cases until it is better refined and proven safe.
It's fine to hoist a glass of rum and eggnog or champagne to toast the festive season, but don't get carried away with your celebratory drinking over the holidays. University of Michigan emergency physicians remind you that even moderate drinking may impair your judgment and result in serious safety and health problems. Alcohol affects the brain and central nervous system, and impairs your ability to function. At the same time, alcohol can give you a feeling of self-confidence or denial that you're being seriously affected by the alcohol.
There's more. Alcohol kills brain cells and can cause memory loss, emotional disturbances, loss of coordination and brain damage. Long-term alcohol abuse can lead to liver cirrhosis and throat, mouth, esophagus, stomach and liver cancers. Then there's the obvious danger of impaired driving. Research shows that people's driving abilities are actually impaired even when they're still below the legal limit for intoxication. The best way to protect yourself from alcohol-related health and safety risks is to avoid drinking or drink in moderation.
An experimental drug with a taste for energy-thirsty cells appears to kill off liver tumors in rabbits. Johns Hopkins University scientists found the chemical, known as 3-bromopyruvate, destroys liver cancer and also shrinks tumors that have spread into the lungs. The substance, which is related to a molecule that occurs naturally in the breakdown of sugar, starves cancerous cells of energy, but appears to leave healthy tissue alone. The researchers say they must confirm the drug's lack of toxicity to normal tissue before they test it in people. However, they add, if it does prove benign, it might offer doctors a promising new therapy for other forms of tumors.
Liver cancer, which has been linked to the hepatitis B virus, strikes about 16,600 Americans a year and accounts for roughly 1 percent of tumor deaths in the United States. However, it's much more common in Asia and Africa, where it makes up half of all cancer fatalities. About 50 percent of patients can be cured of the disease. However, for those with inoperable liver cancer, especially tumors that spread from the colon, surviving a year is a feat. A unique feature of liver tumors is that while they draw their nutrients from an artery, the organ itself is fed separately by the portal vein. In theory, it's possible to target cancerous cells by injecting drugs directly into arterial blood, yet do minimal damage to the surrounding organ. The latest study, published in Cancer Research, attempts such a strategy.
Led by radiologist Dr. Jean-Francois Geschwind, the scientists gave injections of 3-bromopyruvate to rabbits with liver cancer. The potent chemical drains cells of their energy in two ways: by greatly suppressing their ability to use glucose for fuel; and by hindering the ability of internal power plants called mitochondria to make the energy molecule adenosine triphosphate, or ATP. Because cancer cells are lusty for glucose, needing it to support their frenetic growth, a drug that selectively kills tissues that demand sugar will turn this thirst against them. Indeed, a single injection of the drug into the artery supplying the tumors led to "dramatic" shrinkage of the masses, Geschwind says. "By being able to thread a catheter and get close to the tumor, we can deliver agents in much higher concentrations directly to the tumor. You can really kill the tumor that way," he adds. Surprisingly, the healthy cells were spared. "We would have expected some collateral damage, but in this case the specificity of the drug and the method of administering it made a perfect marriage," Geschwind says. The treatment was gentler on normal cells than a current therapy for liver cancer called chemoembolization, in which doctors inject drugs into the tumors while using an oil solution to block off the artery that feeds them.
Some of the rabbits developed liver cancer nodules in their lungs. So the researchers then injected 3-bromopyruvate directly into their bloodstream through a vessel in their ears. Again, the tumors shrank markedly, but the animals appeared otherwise unscathed, says Peter Pedersen, a Johns Hopkins biochemist and a co-author of the study. "We didn't find problems with toxicity, but we don't know what the long-term [outlook] is," Pedersen says. If 3-bromopyruvate ultimately passes the safety tests, Geschwind says it could be useful against a wide range of tumors, because all have the common feature of requiring heaps of energy. However, finding as finely tuned a way to deliver the drug as is possible with the liver will be trickier, he adds.
People with active hepatitis B infections are 60 times more likely to develop liver cancer than those without evidence of the virus, new research has found. The study, reported in New England Journal of Medicine, followed almost 11,900 Taiwanese men who had no initial signs of liver tumors. When hepatitis B enters the body, fragments of the virus, called antigens, can be detected. If a person's blood has HBsAg antigens, they've been infected in the past with hepatitis B. If they have HBeAg fragments, the virus is still infecting their cells. When the liver is infected with hepatitis, its cells undergo rapid turnover, dividing 100 to 1,000 times the normal rate to replace damaged tissue. This process may pave the way for cancerous gene mutations in the organ. It generally takes 20 to 30 years before the toll of hepatitis infection becomes cancer, says Dr. Bruce Bacon, a liver expert at St. Louis University.
Among the Taiwanese men, 111 developed hepatocellular carcinoma, the most common form of liver cancer, within about a decade. In those with no hepatitis, there were 39 cases of liver cancer for every 100,000 person years. For those with HBsAg alone, that rose to 324 cases per 100,000 person years. However, for men with both HBsAg and HBeAg, the number jumped to 1,169 per 100,000 person years. After accounting for other factors that increase the risk of liver cancer, including smoking, alcohol consumption and infection with hepatitis C, a history of hepatitis B infection upped the odds of cancer 9.6-fold and an active hepatitis B infection upped it 60-fold. The researchers also conducted a smaller study in 130 men, and found hepatitis DNA was a strong predictor of liver cancer in men with HBsAG, but not HBeAg. However, they add, since DNA testing for the virus is expensive and requires special lab equipment, screening for HBeAg "may be a more practical way" of trying to estimate the risk of liver cancer.
Marc Ghany, of the National Institute of Diabetes and Digestive and Kidney Diseases, says the findings aren't surprising, since scientists have long known that hepatitis virus triggers liver cancer. However, the Taiwanese study is a smoking gun. "Intuitively, we knew it, but there was not this sort of proof," says Ghany, co-author of an editorial accompanying the journal article. Between 65 percent and 70 percent of people who contract hepatitis B have a form of the virus that spurs the production of HBeAg. The rest are infected with mutant strains that don't have that protein. Yet, Ghany says, those people are still vulnerable to liver cancer if they have the mutant strains, which have become more prevalent and appear harder to treat. An estimated 16,600 people in the United States will be diagnosed with liver cancer this year, and 14,100 will die of the disease, according to the American Cancer Society. Although relatively uncommon in the United States, liver cancer is one of the world's most prolific tumor killers.
Tamoxifen, a popular drug used to treat liver cancer in the developing world, has been found to be harmful to patients in a new Asia-Pacific study. "The study showed conclusively that not only is tamoxifen not benefitting the patient at all ... you are making them worse," Pierce Chow, who headed the nine-country study group said. "Doctors should be discouraged from using tamoxifen" in liver cancer treatment," said Chow, a consultant at Singapore General Hospital.
Liver cancer, which claims 1.25 million lives a year, is endemic among men in the Asia Pacific, he said. Surgery offers the only significant chance of prolonged survival, but only 10 percent of patients discover the disease early enough to be operated on. Most other victims discover the disease in its final stages and are treated with tamoxifen, which has a proven record with breast cancer.
Tamoxifen pills were cheap, costing about 22 Singapore cents (12 US cents) a day, and doctors dispensed it hoping it would work on the liver as well, said Chow. "If you have no proven treatment, you either treat them based on anecdotal evidence or use drugs that have been trialed," he said. "The doctors hoped that if it doesn't do you good, it doesn't do you bad either. That is no longer true."
The findings were drawn from a three-year study of 324 patients in Singapore, Malaysia, Mynamar, South Korea, Indonesia, Thailand, Hong Kong, Australia, New Zealand. A third of the patients were given a placebo and survived an average 2.7 months, another third consumed 60 milligrams of tamoxifen a day and died 2.1 months later, while the remainder took 120 milligrams a day and died after 2.2 months. "It shows that not only does tamoxifen not benefit the patient, it can actually harm them," Chow said, adding the study found there was "no appreciable difference" in the patients' quality of life. Seven previous trials conducted in Western countries had been conflicting and inconclusive, he said.
Chow is to begin a new study on liver cancer patients in January using megace, an alternative drug for breast cancer patients who do not respond to tamoxifen.
Cancer is the fourth biggest killer in Singapore, and it is men who suffer most. The problem confronting doctors and patients alike is that when it is diagnosed, it is already too late. Cancer specialists from 9 countries in the region have come together to decide on the best strategy to tackle this silent killer. Dr Pierce Chow, Consultant (Department of Surgery), Singapore General Hospital, said, "The only proven way of treating this disease is actually surgery, but liver cancer or primary liver cancer being such, most patients are in a stage of the disease where surgery is no longer possible at the moment they are diagnosed by the doctor."
In fact, in most parts of Asia, only 10 to 15 percent of patients can undergo surgery. That leaves the vast majority of sufferers without any options. To try to turn the tide, the first of 3 trials was started 4 years ago with 329 patients from 9 different countries. Associate Professor Lucien Ooi, Chief, (Hepatobiliary Surgery), National Cancer Centre, said, "One of the beauties of doing a study like this is involving many countries, so it's multi-national, multi-centre, and therefore people like from Myanmar for example, from Indonesia, from Australia, from Taiwan who are keen to participate." Strict rules were set to ensure there was consistency. The first 2 studies also looks at Tamoxifen, a drug that has been used for 30 years to treat breast cancer, but now may offer some hope for those people with inoperable liver cancer.
Associate Professor Ooi said, "What we are trying to do in the third study is to try and administer a particular nuclear material, and this would reduce the chance of long term recurrence, hopefully therefore curing the patient of liver cancer." Doctors are expecting the first results in 2 years.
A new drug developed
by Swiss pharmaceutical giant Roche for treating Hepatitis C has been
granted marketing approval by the Swiss regulatory authorities, the company
A four-year research project in China has shown that Maotai, the most famous brand of Chinese liquor can effectively combat hepatic fibrosis and hepatocirrhosis. The liquor causes the liver to produce 22 times more metallothioneine than normal, which is believed to prevent the formation of hepatic fibrosis. Metallothioneine and superoxide dismutase, another element in Maotai, can remove free radicals in human body and combat tumours.
Medical examinations conducted on 99 workers at the Maotai liquor plant in southwest China's Guizhou province, who drink an average of 250 grams of Maotai per day, found no cases of hepatic fibrosis or hepatocirrhosis. Maotai is rich in proteins, vitamins and aminophenols.
Research results also showed a low rate of gastric ulcers and digestive system diseases among Maotai drinkers. Maotai made its reputation at an international exposition in 1915, and has become a popular alcoholic drink for important occasions.
A method for treating
liver cancer with tiny radioactive glass beads, developed by researchers
at the University of Missouri-Rolla and the University of Missouri-Columbia,
has been approved for use in the United States. The first patients to
be treated with radioactive glass beads, now marketed under the name TheraSphere
by MDS Nordion, will be treated later this year at the Mayo Clinic in
Rochester, Minn., and at the University of Pittsburgh School of Medicine.
The treatment consists
of injecting millions of tiny, radioactive glass beads into the main artery
supplying blood to the liver. The blood carries the beads into the liver,
where they deliver localized radiation to malignant cells in liver tumors.