The frequency of post-operative complications following surgery for liver cancer is associated with a hospital having a low volume of liver surgery. Investigators at The Cancer Institute of New Jersey (CINJ) are presenting that finding at the 63rd Annual Society of Surgical Oncology Symposium taking place this week in St. Louis. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

Previous analyses of state and national databases have documented institutional volume-related death rates at low-volume hospitals for this type of surgery; however, a causal relationship has not been determined. In this current study, the team analyzed 9,289 cases between 1998 and 2007 from the Nationwide Inpatient Sample database. Patients were more than 18 years old and underwent elective surgical removal of a portion of their liver due to malignancy. A threshold of 20 annual liver surgeries was used in each hospital to separate low-volume facilities from high-volume facilities. Investigators reviewed postoperative complications such as sepsis and hemorrhaging, as well as problems with the liver, lungs, heart, and bladder. Also taken into account were socio-demographic factors such as age, gender and race among other variables.

What they found was that patients at low-volume hospitals experienced at least one of the analyzed postoperative complications more often than at high-volume facilities. Specifically, hemorrhagic, septic and lung complications were more likely to occur at low-volume institutions. However, overall, the rate of liver complications was lower at these facilities. When mortality was analyzed, it was found that patients who underwent liver cancer surgery at low-volume hospitals were 1.4 times as likely to die as patients who had the procedure at a high-volume institution.

Christopher J. Gannon, MD, surgical oncologist at CINJ and assistant professor of surgery at UMDNJ-Robert Wood Johnson Medical School, is the lead investigator. “This new data is significant in that it could be utilized in low-volume facilities to investigate systems problems once complications occur. This information also has benefit for high-volume hospitals, as it could also be used in centralizing liver cancer care,” he noted.

Over 60 per cent of Canadians are classified as overweight or obese. This epidemic is a concern for experts around the world. One of the major problems is high levels of lipids in the blood, which can lead to cardiovascular disease, fatty liver disease and Type 2 diabetes. But a University of Alberta researcher has taken a major step in protecting people against these diseases.

Richard Lehner and his research group found that decreasing the activity of an enzyme called triacylglycerol hydrolase, or TGH, in an animal model results in lowering the amount of fat in the blood and improves glucose metabolism. It also appears to keep fat from being deposited into organs that aren’t meant to store fat, like the liver.

A lack of TGH also showed to protect the beta cells in the pancreas that produce insulin and this can potentially protect from the development of diabetes in obese patients.

The benefits don’t end there. Animal models that lack the enzyme also showed to burn more fat and were more physically active compared to those who had the enzyme.

This discovery shows that TGH could eventually be used as a target for pharmaceuticals to combat metabolic complications associated with obesity.

A new study has found that chlorophyll and its derivative chlorophyllin are effective in limiting the absorption of aflatoxin in humans. Aflatoxin is produced by a fungus that is a contaminant of grains including corn, peanuts and soybeans; it is known to cause liver cancer – and can work in concert with other health concerns, such as hepatitis.

Levels of aflatoxin are carefully regulated in the United States, but are often found in the food supplies of developing nations, especially those with poor storage facilities.

OSU scientist George Bailey, a distinguished professor of environmental and molecular toxicology, pioneered studies of aflatoxin in China, where he found that in one region, one out of every 10 adults died from liver cancer.

But what has the science world particularly intrigued with this follow-up study is the methodology used by the researchers – a new “Phase 0″ approach that safely tests low levels of carcinogens in human volunteers to measure the total aflatoxin exposure and to determine the effect of dietary chlorophlls on reducing this exposure.

Results of the study were just published in the journal Cancer Prevention Research.

Bailey and several other researchers, including lead author Carole Jubert, were part of the recent study. The journal also included a perspective written by a pair of Johns Hopkins researchers – Thomas Kensler and John Groopman – who praise the methodology and suggest that these Phase 0 “microdosing” studies should be expanded.

They wrote: “…microdosing studies with carcinogens have the potential to provide important insights into chemopreventive interventions and to enhance the overall clinical development and safety evaluation of preventive agents.”

The Phase 0 study “…may open the door for all kinds of new research,” said Jubert, a former researcher in Bailey’s lab at OSU’s Linus Pauling Institute. Jubert now works for Life Microsystems, an OSU spinoff company that hopes to continue work with natural products grown in Oregon, including pure chlorophylls.

“The technology is not particularly difficult,” she added. “It’s just a novel approach to evaluate toxin exposure in humans.”

In their study, Jubert and her colleagues gave very low doses of aflatoxin labeled with carbon-14 isotopes as a tracer to four human volunteers. They then gave the volunteers the same doses of aflatoxin along with doses of either chlorophyll or chlorophyllin, which previously had been shown to reduce carcinogen bioavailability in trout and rats. Using an accelerator mass spectrometer, they measured the rate of aflaxtoxin bioavailability. This technique is extremely sensitive, the researchers say, allowing measurement of minute amounts of any labeled compound.

Their research revealed rapid absorption of aflatoxin, which was significantly limited after the chlorophyll and chlorophyllin treatments.

“The beauty of this kind of ‘Phase 0′ study is the use of ultra-sensitive technology and ‘microdoses’ of environmental carcinogens to study toxicokinetics within the human body,” said John Mata, an OSU pharmacologist and second author on the study. “These measurements can be important because they allow us to better design future studies to understand the effects of dietary constituents on cancer risk.

“In this case, clearly the results merit further study,” Mata added. “We showed that aflatoxin is absorbed quite rapidly and that chlorophyll and chlorophyllin have an ameliorating effect, preventing the toxin from getting into the bloodstream. Further studies can more precisely explore the interactions, as well as dosage levels.”

Jubert and Mata also have tested the feasibility of using similar technology on human exposure to other toxins, including smokers who ingest carcinogens through cigarette smoke.

Mata, a professor in OSU’s College of Veterinary Medicine, is a pharmacologist who previously worked in the drug industry. He said Phase 1 studies are designed to see if a compound is safe; Phase 2 expands the scope of the project, and Phase 3 looks at the compounds’ efficacy. Phase 0 represents a new concept – a way to measure the kinetics of a drug by using extremely small doses that pose little risk to the volunteers.

In this case, the amount of radiation given the human volunteers was equal to that you would encounter from a one-hour airplane ride; the level of aflatoxin administered was 1/30th the amount the Food and Drug Administration allows in a peanut butter sandwich.

Facing the increasing prevalence of type 2 diabetes worldwide in the past few decades, one may ask what is wrong with humans. Geneticists tell us that the human genome has not changed markedly in such a short time. Therefore, something must be happening in our environment or diet. As a matter of fact, dietary pattern is known to be closely linked to the development of type 2 diabetes. The increasing prevalence of type 2 diabetes following worldwide food fortification with niacin suggests that type 2 diabetes may involve excessive niacin intake.

A research article published in the World Journal of Gastroenterology addresses the association between nicotinamide overload and type 2 diabetes. The study revealed that diabetic patients have a slow nicotinamide metabolism and thus require a longer time to clear up excess nicotinamide metabolites within the body. High nicotinamide intake may lead to an increase the generation of reactive oxygen species, and subsequent oxidative stress and insulin resistance, both being the major features of type 2 diabetes. The liver is the main organ responsible for nicotinamide detoxification. This study found that liver-injury-inducing drugs may reduce nicotinamide detoxification and thus impair glucose tolerance. Most interestingly and importantly, this study demonstrates that sweating is an effective way for expelling excess nicotinamide from the body. The findings from this study may help explain a wide variety of well-documented but poorly understood phenomena in diabetes, such as lifestyle-triggered diabetes, liver-disease-related abnormal glucose metabolism, post-burn insulin resistance, and seasonal diabetes.

Nowadays, the high prevalence of type 2 diabetes may be due to both too much niacin in our foods and too little excretion through our sweat glands. The so-called gene-environment interaction in type 2 diabetes may actually be the outcome of the association of excess niacin intake and relatively low detoxification and excretion from the body, says lead author Dr. Shi-Sheng Zhou, Professor of the Institute of Basic Medical Sciences of Dalian University.

Historically, niacin deficiency was restricted mainly to those with poor nutrition who performed heavy industrial labor. Hence, this study gives rise to an important social and public health issue whether foods need to be fortified with niacin any more, when the people in developed countries have already been living in an age of over-nutrition. The authors found that reducing nicotinamide intake and facilitating the excretion of nicotinamide metabolites may be a useful preventive and therapeutic intervention in type 2 diabetes.

Research published in the current issue of the journal, Clinical Science, appears to have found a link between obstructive sleep apnoea and non-alcoholic steatohepatitis. Dr Anne-Christine Piguet and colleagues from the University of Bern, Switzerland, kept mice for a week in low-oxygen atmospheres and found that it led to increased levels of fat and inflammation in their livers.

Apnoea means “without breath” and occurs when the muscles in the airways behind the tongue relax in sleep, causing the person to snore and briefly, to stop breathing.

Nonalcoholic steatohepatitis (NASH) is a common, often “silent” liver disease occurring in around 40% of the population. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly.

Obesity predisposes patients to both fatty liver diseases and obstructive sleep apnoea.

To mimic the effects of low oxygen levels caused by the repeated obstruction of the upper airways in sleep apnoea, the researchers kept mice in a low oxygen environment for seven days. After this time they were found to have more fat and inflammation in their livers compared to mice that had been kept in atmospheres with normal levels of oxygen. When the mice were exposed to low oxygen levels, the genes that controlled fat synthesis in the liver seemed to be more active while those that controlled fat breakdown demonstrated reduced activity.

In addition, the mice exposed to low levels of oxygen became less sensitive to insulin. This is the mechanism by which the body regulates blood sugar and is a cause of diabetes. Metabolic disorders such as diabetes and obesity can cause complications in patients with NASH.

Commenting on the finding, Dr Piguet said, “Hypoxia (lack of oxygen) may be the link leading to accumulation of fat in the liver and to the progression of non-alcoholic steatohepatitis. Our findings show that it is important both to screen obese patients for obstructive sleep apnoea to prevent it contributing to fatty liver disease and to treat those patients who already have NASH for hypoxia which may be making their condition worse”.

In patients with unresectable (unable to be removed by surgery) liver cancer, an interventional radiology procedure called triple-drug transcatheter arterial chemoemobolization (TACE) followed by a liver transplant may significantly increase a patient’s chance of long-term survival, according to a study published in the December issue of the American Journal of Roentgenology.

Liver cancer is the fourth most common cancer in the world and is responsible for more than 500,000 deaths worldwide annually. During triple-drug TACE, anti-cancer drugs are injected directly into the blood vessel feeding a cancerous tumor. An embolic agent is placed inside the blood vessels that supply blood to the tumor, in effect trapping the chemotherapy in the tumor.

The study, performed at the David Geffen UCLA School of Medicine in Los Angeles, included 124 patients with unresectable liver cancer. Twenty-eight patients underwent triple-drug TACE followed by a liver transplantation; 96 patients underwent triple-drug TACE only. “In our study, patients who underwent triple-drug TACE followed by liver transplantation showed the longest survival,” said Antoinette S. Gomes, M.D., lead author of the study. The median survival in the transplant recipient group was 112.80 months. In the no-transplant group, the median survival was 15.75 months.

“Until recently, there has been considerable controversy regarding the benefits of emobolization therapy in patients with unresectable liver cancer,” said Gomes.

“In our series, survival after TACE was best in patients who ultimately underwent liver transplantation. However triple-drug TACE alone still improved survival in patients who did not undergo a liver transplantation,” she said.

Scientists in China are reporting discovery of unusual liver proteins, found only in males, that may help explain the long-standing mystery of why the hepatitis B virus (HBV) sexually discriminates — hitting men harder than women. Their study has been published online in ACS’ Journal of Proteome Research, a monthly publication.

Shuhan Sun, Fang Wang and colleagues note that chronic hepatitis B seems to progress and cause liver damage faster in men, with men the main victims of the virus’s most serious complications — cirrhosis and liver cancer. Men infected with HBV also are 6 times more likely than women to develop a chronic form of the disease. About 400 million people worldwide have chronic hepatitis B, including a form that is highly infectious and can be transmitted through blood, saliva, and sexual contact.

In experiments with laboratory mice, the scientists found abnormal forms of apolipoprotein A-I (Apo A-I), a protein involved in fighting inflammation, in the livers of infected male mice but not infected females. They then identified abnormal forms of these Apo A-I proteins in blood of men infected with HBV, but not in women. In addition to explaining the gender differences, the proteins may provide important markers for tracking the progression of hepatitis B, the scientists suggest.