February 14, 2012

Does Anesthesia Alter Tumor Recurrence?

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By: Travis Giddings  Reviewed By: Joseph V. Madia, MD

Published: Feb 13, 2012 07:20 pm

Anesthetic choice changes liver cancer recurrence

(dailyRx) Occasionally, studies of medical data find unexpected trends. Recently, an analysis of anesthetic use during liver surgery found a surprising relationship for tumor recurrence.

A study of medical records over a nine-year period revealed that general anesthesia was associated with fewer recurrence of tumors in liver cancer.

But despite the difference, there was no significant difference in mortality between the two groups.

A group from China studied whether anesthetic technique made any difference in a specialized surgery known as radiofrequency ablation, where surgeons use radio waves rather than scalpels to destroy tumors. Radiofrequency ablation may be used for surgery in difficult areas to access, or when a minimally invasive technique is preferred.

Documented by Renchun Lai, M.D., of Sun Yat-Sen University Cancer Center in Guangzhou, the recurrence of liver tumors was lower in patients who had regional anesthesia instead of general anesthesia.

Dr. Lai examined the outcomes of 179 patients who underwent radio frequency ablation for small liver tumors, comparing general anesthesia in 117 patients to epidural anesthesia in 62.

The authors of the study called for randomized clinical trials to investigate further for the true cause of the relationship between anesthesia use and reduced tumor recurrence. Theories ranged from a direct effect of the anesthesia on the tumor cells or even the immune system itself, but the finding could reflect decisions by surgeons on which anesthesia to use on a case by case basis.

"Such retrospective studies are very difficult to interpret because it is impossible to understand what risk factors were not evenly distributed among the patients," commented Steven L. Shafer, M.D., of Columbia University, Editor-in-Chief of Anesthesia & Analgesia.

Other professionals believed that the anesthesia itself could be the cause. "There is overwhelming mechanistic support for regional analgesia protecting against cancer recurrence, along with strong animal data," commented Daniel I. Sessler, M.D., chair of Outcomes Research at The Cleveland Clinic.

"We and others have published both positive and negative retrospective studies. But all are small and suffer all the substantial limitations of observational analyses. Resolution of the question will have to await the results of randomized trials, including ours."

A separate study published in 2005 found that the costs of regional and general anesthesia were similar overall, with some variations of 10 percent in either direction depending on the characteristics of the individual surgery.

Results were published in the journal Anesthesia & Analgesia. Authors of the study declared no conflict of interest.


Liver Cancer (Hepatocellular Carcinoma)

The American Cancer Society estimates that there are over 26,000 new cases of primary liver cancer and bile duct cancer in the United States each year, and they are responsible for over 19,000 deaths. The average man has about a 1% chance of developing this cancer over his lifetime, while the average woman has about a half percent chance.

Primary liver cancer most commonly includes hepatocellular carcinoma (HCC) and can coexist with cholangiocarcinoma, a cancer of the bile ducts between the liver and gall bladder. It is important to note that most cases of cancer in the liver are metastases from other cancers, such as those from the colon, breast, or prostate. Primary liver cancers begin in the liver itself. Other less common forms of primary liver cancer include angiosarcomas and hemangiosarcomas (cancers that begin in the blood vessels of the liver), lymphoma of the liver, and hepatoblastoma (a rare pediatric cancer usually occurring in children under three years of age). There are also several variants of benign liver tumors. Hepatocellular adenomas (a benign liver tumor associated with oral contraceptive use and glycogen storage disease) must be watched closely, as they have a potential to turn cancerous.

Hepatocellular carcinoma, the most common form of liver cancer, is strongly associated with infection by chronic hepatitis B and C. These infections cause liver cancer more often in Asian and African countries where hepatitis viruses are endemic and people acquire the disease early in their life.

Cases of liver cancer in the United States have tripled over the past three decades. While the most common cause of liver cancer used to be from alcohol abuse and the resulting cirrhosis of the liver, hepatitis C infection is now a leading cause. Obesity, particularly fatty liver disease, is also implicated. Other causes include hemochromatosis (a disease that causes the body to store too much iron), high exposure to aflatoxins (a mold found in peanuts, rice, soybeans and corn; rare in developed countries), and Type 2 diabetes.

Symptoms of HCC usually present with classic signs of liver dysfunction such as jaundice (yellowing of the skin due to too much bilirubin), bruising and blood clotting problems (due to the liver making the clotting factors in our blood), and ascites (fluid buildup in the abdomen from liver dysfunction). Other general symptoms include nausea, fatigue, vomiting, and unintentional weight loss.

In patients who are at high risk for HCC, screening is usually done with ultrasound and CT scan, as well as MRI. While there is no reliable blood test for liver cancer screening, a high level of alpha-fetoprotein (AFP) should be considered suspicious for liver cancer. Liver biopsy is also done, although this is not necessary for diagnosis if imaging is definitive.

Treatment for HCC is difficult, as many patients with liver cancer also have damaged livers from cirrhosis. Treatment must be balanced between treating the cancer and also mitigating the risk of liver failure. Early stage cancer has the potential for surgical removal, however most cases of liver cancer are discovered when they are advanced, making surgery difficult. Other treatments are dependent on the size and location of the tumors, such as ethanol injection into the tumor (small tumors), radiofrequency ablation (using high-frequency radiowaves to destroy the tumor), transcatheter arterial chemoembolization (cuts off the blood supply to unresectable tumors), and cryosurgery (destroying cancerous tissue with subzero temperatures). Liver transplantation is a relatively successful option for patients without metastatic spread. Sorafenib (marketed as Nexavar) is a tyrosine kinase inhibitor that has shown efficacy in treating HCC.

Ultimately, HCC is a difficult cancer to treat and survival rates are low, with most cancers being unable to be completely removed. These patients usually succumb to the disease within three to six months. Across the board, patients with a solitary small tumor of less than three centimeters in size have a five-year survival rate of 20%. Patients with advanced disease have a one-year survival rate of 30%.

Prevention of liver cancer is extremely effective if vaccinated against hepatitis B. Avoidance of alcohol abuse is also effective. Other patients with different causes of cirrhosis or chronic liver inflammation will benefit from routine ultrasound screening and AFP measurements in the hope of detecting cancer early.

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