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A new study reveals patients with liver cancer who have no other treatment options might benefit from more aggressive operations once considered too risky, report University of Florida scientists, who also published research this month yielding insight into ways to protect the liver during surgery.

The number of Americans battling liver disease, meanwhile, is expected to increase, especially as the obesity and diabetes epidemics fuel conditions that damage the organ, UF researchers say. One in 10 Americans currently has liver disease, according to the American Liver Foundation, and liver disease often contributes to the development of cancer. The American Cancer Society estimates that 21,370 new cases of liver cancer and 18,410 related deaths will occur this year.

Surgeon Alan Hemming, M.D., chief of transplantation and hepatobiliary surgery at UF’s College of Medicine, has shown that using a more aggressive approach to liver surgery can prove successful in patients who were deemed inoperable by traditional standards.

“We are doing things that are very complex that could not be done a few years ago and yet getting the same success rates that standard, less complex liver surgery was getting 10 years ago,” said Hemming. “If you are a patient who is told you only have six months to live and there are no options but then all of a sudden you are given a more than 30 percent chance of survival with admittedly complex surgery, you would think that is a good option.”

Published in this month’s Journal of the American College of Surgeons, Hemming’s 10-year retrospective study focuses on 116 patients who were initially told by an outside hospital routinely performing liver surgeries that they were not candidates for an operation. These patients ultimately underwent more aggressive surgery at Shands at UF medical center. Approximately one-third of patients survived five years or more, despite an initial prognosis that they had just a few months to live.

UF surgeons used a combination of surgical techniques taken from both transplantation and surgical oncology, including chemotherapy, performing procedures in stages, reconstructing the liver’s vascular system and using surgery and radiofrequency ablation together, said Hemming, who directs the UF Center for Hepatobiliary Disease.

"Surgical removal of liver tumors offers the best chance at long-term survival for patients with cancers of the liver,” said Todd W. Bauer, M.D., a surgical oncologist at the University of Virginia School of Medicine. “Over the past 10 years, significant advances have been made in the field of liver surgery which allow surgeons to perform potentially curative resections more safely for a greater number of patients and with better long-term survival. These outstanding results by Dr. Hemming and colleagues fully illustrate this progress.”

Hemming said the work UF basic science researchers are conducting to identify ways to protect the liver during surgery also could help increase the number of patients who could benefit from liver surgery and possibly make more livers viable for transplantation.

Although unique because of its ability to regenerate, the liver is actually quite delicate and can easily be irreversibly damaged during surgery or transplantation. Composed of a large amount of blood — approximately 20 percent — the liver is greatly affected when the blood supply is cut off during surgery. This causes ischemia, which leads to a lack of oxygen to the organ.

“Paradoxically, ischemia is OK, but the real problem is when blood returns to the liver,” said principal investigator Jae-Sung Kim, Ph.D., a UF assistant professor of surgery and of pharmacology and therapeutics.

As blood and oxygen flood the organ, the natural process by which cells eliminate their own weakened components to increase their longevity — called autophagy — malfunctions, causing damaged cells to build up within the liver.

So far, attempts to limit the effects of this type of injury have not been successful. UF study findings published this month in the journal Hepatology reveal the underlying problem is caused by more than one factor and that the cell’s “power plant,” known as mitochondria, is one of the crucial elements.

“We found that if we use the autophagy process and selectively remove damaged mitochondria, it actually keeps the cell alive after the oxygenated blood is delivered back to the liver,” said Kim.

In animal studies, UF researchers found the activation of a key enzyme that is naturally produced when oxygen returns to the liver depletes two proteins that help regulate the cell’s ability to dispose of its weakened elements.

“As cellular levels of these proteins are depleted, cell and tissue lose control, and the liver loses viability,” Kim said.

Kim said the next step is to work with pharmacologists to develop drug treatments that will bolster the proteins to keep the cell’s natural house-cleaning process on track, preventing cellular injury and improving liver function after surgery.

Bauer added that this research moves the field one step closer to identifying drugs that could prevent liver damage during surgery, helping to reduce complications at a time when liver disease is on the rise.

“Since liver diseases are steadily increasing due to increased prevalence of metabolic diseases such as diabetes, fatty liver and obesity, more patients may need liver surgery in the near future,” Kim said.