Liver Cancer

A common cancer

By PAUL YEO
starhealth@thestar.com.my

Sunday June 19, 2011

THE liver is the second largest organ in the body, and performs a variety of functions that are vital to life. These include the filtering and processing of blood; bile production; producing proteins, glucose and cholesterol; storing fat-soluble vitamins, glycogen and iron; metabolising drugs, glucose and haemoglobin; and even a role in immunity.

That’s an impressive resume, and it’s safe to say that when something adverse happens to the liver, life as we know it will never be the same.

Unfortunately, many things can go wrong in the liver, and probably the worst of the lot would be cancer.

In fact, liver cancer is the sixth most common cancer worldwide. Worse, it’s the third most common cause of cancer-related death. This is probably due to the fact that there are typically no symptoms of the disease until the cancer is in its later stages.

Dr Mellor ... Those living with hepatitis C, hepatitis B viral infection, as well
as those with alcohol-related cirrhosis, are at most risk of developing chronic,
cirrhotic liver disease. Hence, they are ultimately at higher risk for hepatocellular carcinoma (liver cancer)

 Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and is responsible for about 90% of the primary malignant liver cancers seen in adults.

The current five-year survival rate for patients with liver cancer are as follows: Europe, 8.6%; United States, less than 10%; and Asia, less than 10%, for inoperable tumours. These are very depressing figures indeed.

According to consultant oncologist Dr Matin Mellor, approximately 75 to 80% of all HCC occurs in Asia. “In some parts of Asia and Africa, HCC is the leading cause of cancer mortality.”

Risk factors

It has been noted that liver cancer disproportionately affects men, with about three times as many men developing the disease as women.

Although the overall cancer incidence and mortality are decreasing in the United States, both the incidence and mortality of liver cancer are increasing worldwide.

There are a few major risk factors for the development of the disease, but the most significant one is chronic, cirrhotic liver disease. Cirrhosis is the widespread disruption of normal liver structure by fibrosis and the formation of regenerative nodules that is caused by various chronic progressive conditions affecting the liver, such as alcohol abuse.

“Those living with hepatitis C (HCV), hepatitis B viral infection (HBV), as well as those with alcohol-related cirrhosis, are at most risk of developing chronic, cirrhotic liver disease. Hence, they are ultimately at higher risk for HCC.

“Worldwide, 75 to 80% of HCC cases are related to chronic HBV or HCV infection,” noted Dr Mellor.

Other risk factors include:

·Obesity – non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

·Diabetes

·Long-term exposure to aflatoxins (naturally occurring toxins produced by many species of fungus that can be found in tree nuts, peanuts and other oilseeds).

·Tobacco use

·Long-term use of anabolic steroids.

·In some parts of the world, water contaminated with arsenic.

Symptoms and complications

It is often said that the symptoms of liver cancer only appear late into the disease. The signs and symptoms may include the following:

·Unexplainable weight loss

·Ongoing lack of appetite

·Feeling very full after a small meal

·A hard lump on the right side just below the rib cage

·Pain around the right shoulder blade

·Yellow-green colour to the skin and eyes (jaundice)

·Discomfort in the upper abdomen on the right side

·Unusual tiredness

·Nausea

Many of these symptoms can also be an indication of liver cirrhosis.

Liver cirrhosis leads to many complications. There can be fluid accumulation in the abdomen (ascites), risk of infection to the lining of the abdomen (bacterial peritonitis), enlarged spleen, distended and/or swollen veins, brain dysfunction (hepatic encephalopathy), malnutrition, and of course, HCC.

According to Dr Mellor, HCC usually presents in patients aged 40 to 50 years old, and about 40% of these patients do not show any symptoms during diagnosis.

“Diagnostic tests for HCC include a full history and examination, liver function tests, ultrasound and other forms of radiology such as CT or MRI scan, and tumour markers (in the case of HCC, it’s alpha-fetoprotein serology).

“Once a diagnosis is confirmed, the cancer is then staged. Staging is used to determine prognosis and guide treatment,” said Dr Mellor.

“Staging HCC is difficult because most patients have underlying liver disease, and key prognostic indicators are not clearly defined. In addition, there isn’t a universal satging system that is used worldwide. There are a few around, and it depends on the doctor’s personal choice as to which one is used.

“But in general, the guidelines recommend that HCC staging systems should consider the tumour stage, liver function, health status, and impact of treatment,” he added.

Prognosis and treatment

A person’s prognosis depends on both the extent of liver disease, as well as the cancer. In general, a majority of patients present with intermediate or advanced disease, which does not bode well for future prognosis.

Treatment options for liver cancer depend on the stage of the malignant disease, underlying liver function and the patient’s overall condition.

Surgery offers the best chance to cure patients with liver cancer. If the cancer is found at an early stage and the rest of the liver is healthy, surgery with or without liver transplantation may be curative. However, only about 15% of patients are operable.

“For early stage HCC, surgery (which could be partial or total removal of the liver), or other techniques such as percutaneous ablation (a needle probe is inserted into the liver tumour, usually under ultrasound, CT or MRI, and radio-frequency oscillations used to kill liver cancer cells).

“For the intermediate stage, transarterial chemoembolisation (TACE) is used,” Dr Mellor explained.

TACE exposes the tumour to high concentrations of chemotherapy and confine the agents locally as they are not carried away by the bloodstream. At the same time, this technique deprives the tumour of its needed blood supply, which can result in the damage or death of the tumour cells.

Treatment options for advanced patients are limited. There is a drug, sorafenib, which is the first approved systemic therapy for HCC, and the only one shown to significantly improve overall survival in patients with the disease.

References:

1. World Health Organization. Hepatitis B. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/. Accessed May 8, 2008.

2. Mayo Clinic. Liver Cancer. Available at: http://www.mayoclinic.com/invoke.cfm?objectid=C2850661-4805-4AD6-905AD30E9FC79DB2&dsection=5. Accessed May 8, 2008.

3. International Agency for Cancer Research. GLOBOCAN 2002. Available at: http://www-dep.iarc.fr. Accessed May 12, 2008.

4. Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004. Available at: http://www-dep.iarc.fr. Accessed May 12, 2008.

5. Berrino et al., “Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study.” The Lancet Oncology 2007: 8: 773-783.

6. American Cancer Society. What are the Key Statistics About Liver Cancer? Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_liver_cancer_25.asp?sitearea==. Accessed May 8, 2008.

7. Teo, T.K. and Fock, K.M. “Hepatocellular Carcinoma: An Asian Perspective.” Digestive Diseases 2001:19: 263-268.

8. National Cancer Institute. Cancer of the Liver and Intrahepatic Bile Duct. Available at: http://seer.cancer.gov/statfacts/html/livibd_print.html. Accessed Accessed May 8, 2008.

9. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site, 2007.

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The drug that could
A life worth living
The NexPAP programme

http://thestar.com.my/health/story.asp?file=/2011/6/19/health/8924507&sec=health

Treating liver cancer

By LIM WEY WEN
starhealth@thestar.com.my

Sunday September 25, 2011

Beyond surgery, treatment options for liver cancer often involve injecting a cancer-destroying agent into the organ.

DESPITE the increasing availability of cancer treatments in hospitals worldwide, liver cancer remains one of the more difficult cancers to treat.

Regardless of its origins (whether it starts in the liver, or is a cancer that has spread to the liver), in a lot of cases, conventional therapies like surgery, systemic chemotherapy, and external radiotherapy, are not suitable treatments.

Systemic chemotherapy – the consumption or injection of anti-cancer drugs that travel through the whole body – often does not work well for liver cancer.

(From left) Prof Sangro, Prof Chow, Dr Lee and Prof Lau sharing their
experiences with SIRT at the press conference in Hong Kong.

(From left) Prof Sangro, Prof Chow, Dr Lee and Prof Lau sharing their experiences with SIRT at the press conference in Hong Kong.

External radiotherapy, on the other hand, is not suitable because normal liver cells and the organs surrounding the liver are very sensitive to radiation.

Finally, surgery, the only method that has the potential to “cure” liver cancer by removing it, can only be done for an estimated 10 to 30% of patients because it is only suitable for those who have relatively good liver function with small tumours located within the liver.

“When patients can go for surgery for liver cancer, it really confers long-term survival,” says Singapore General Hospital head of the hepato-pancreatobiliary surgery team Prof Pierce Chow. “But the thing with most liver cancer patients is that although surgery is very good, when they are diagnosed with this cancer, they are already at the stage of the disease where surgery is not possible.”

However, not all is lost. As doctors and scientists work to overcome the challenges involved in treating liver cancer, more treatment modalities are starting to emerge as viable therapies.

Instead of “poisoning” cancer cells with systemic chemotherapy, or “burning” them with external radiation, doctors can now inject cancer-destroying agents directly into the liver through the arteries that supply blood to it. These agents work by either killing the cancer cells or blocking and destroying the arteries – the blood vessels that nourish them (see Treatment options).

One of these therapies is radioembolisation (RE), or Selective Internal Radiation Therapy (SIRT).

In SIRT, interventional radiologists (doctors who specialise in radiology) will pass a catheter through an artery near their patient’s groin to reach the small blood vessels (arterioles) that supply tumours in the liver. Once the catheter reaches the arterioles that feed the tumours, the doctors will release radioactive beads (called microspheres) into them.

While the microspheres can pass through the arterioles, they are too large to pass through the capillaries that come after the arterioles. These microspheres will then lodge in the arterioles, where the radioactive material in the beads (like Yttrium-90) release a high dose of radiation over time and kill the surrounding cancer cells.

Although the technology has already been researched and developed in the 1980s, it has only gained increasing clinical interest in the past decade.

“In the 1980’s and 1990’s, studies were done on animals to make sure the treatment is safe,” says one of the researchers of the technology, professor of surgery at The Chinese University of Hong Kong medical faculty, Prof Joseph Lau. After that, studies on its safety and appropriate dose ensued.

Since 2000, it has been used in patients who have failed other therapies. In Malaysia, it has been available since 2007.

Prof Lau and Prof Chow were speaking at a press conference called by Sirtex, an Australian based medical device company that produces the tiny radioactive microspheres used in SIRT, at the sidelines of the recent fifth annual conference of the International Liver Cancer Association in Hong Kong.

Together with Taipei Veterans General Hospital attending physician in radiology Dr Rheun-Chuan Lee, and University of Navarra School of Medicine professor of medicine Prof Bruno Sangro, they were there to present some of their experience and latest findings on SIRT.

Prof Sangro, who conducted a retrospective study that evaluates the medical records of 325 patients in eight centres across Europe, found that the treatment was reasonably well tolerated. Some of the side effects include fatigue (in 54% of patients), nausea or vomiting (32%), abdominal pain (27%) and fever (12%).

In his study, about half the patients – who are mostly male (81%), ranging from 22 years old to 87 years old, with liver cancer from the early stages to the advanced and terminal stages – survived more than 13 months after the treatment.

About 16% of them lived up to three years after.

“The main factors that influence the survival of a patient, is the liver function before the treatment, and also how advanced and aggressive the tumour was,” says Prof Sangro. In other words, a patient’s prognosis is worse if they have more tumour or tumours that have spread, poor general health, or liver dysfunction before the treatment.

Prof Sangro’s study, called the ENRY (European Network on Radioembolisation with Yttrium-90 Resin Microspheres) study, is one of the largest studies published on the treatment to date.

Despite some studies that find the median overall survival of patients treated with SIRT comparable to those treated with conventional therapies like transarterial chemoembolisation (TACE) and radiofrequency ablation (RFA), many doctors are still turning to it when these treatments fail, or are not suitable.

This is partly due to cost considerations and the lack of data to show that it could be used as a first-line treatment.

In Taiwan, SIRT is only used when the patient’s tumour invades the main blood supply of the liver (the portal vein) or does not respond to conventional therapies like TACE because SIRT is not covered under the national health insurance in the country.

Says Dr Lee, patients who are treated with TACE need more sessions of treatment (about three to six sessions) compared to SIRT (usually only once), and patients treated with SIRT tend to have less post-embolisation syndrome (like nausea or vomiting, fatigue, abdominal pain). However, he reckons that SIRT is a much more complex procedure.

To find out whether SIRT can be used as a first-line treatment for patients with advanced liver cancer who have failed conventional therapies, Prof Chow is now part of an Asia Pacific phase III randomised controlled trial to compare SIRT with sorafenib, an oral drug used to treat patients with advanced liver cancer who have failed conventional therapies.

“At the end of the trial, we will be able to see which of these two therapies should be used as a first-line therapy for these patients,” says Prof Chow.

Like many cancer treatments, SIRT is not suitable for everyone. Commenting on the press conference, Dr R. Kananathan, a Malaysian consultant oncologist in private practice reckons that a patient’s laboratory results need to show that they have relatively good liver function and general health to ensure that it is safe to perform the procedure.

After that, interventional radiologists will need to perform a special scan using radioactive material to determine the amount of radiation that is likely to pass through the liver to the lungs (“shunting”) before radioactive microspheres can be delivered into a patient’s liver.

They will proceed only if the amount of radiation that has passed through is less than 15%, says Dr Kananathan.

Back in Kuala Lumpur, Fit4Life asked consultant vascular and interventional radiologist Dr Alex Tang for some comments on the procedure. Dr Tang says that while SIRT is very useful in large or multiple small hepatomas (liver tumours) in the intermediate or advanced stages (that are limited to one or two lobes of the liver), it does come with “a lot of catches”.

Besides the cost factor, it is also a very technically challenging procedure and errors can bring about serious complications.

That being said, Dr Tang does not view the procedure as a last resort when all else fails. “I’d say we should offer the procedure before the liver is too weak,” he says.

However, a patient has to be assessed carefully in terms of his or her clinical status, disease status, and financial status, as well as the possible clinical outcomes and complications before the best option is suggested.


http://thestar.com.my/health/story.asp?file=/2011/9/25/health/9506844&sec=health

See also:

Tumour killed in breakthrough Treatment
Human Initiated Therapeutic Vaccine  >>> HITV
Healing Illness - A Natural Anti-Cancer Protocol
Cancer fighting articles on this blog
Alternative Cancer treatment articles on this blog

May be of interest:

Dendritic Cell Treatment  >>>  DCT

Kidney & Liver Cancer - Treatment options

Treatment options

Sunday September 25, 2011


AS a total eradication, or cure, of cancers are often rare, the main goals of cancer treatment is to “downstage the lesion, arrest the progression, alleviate symptoms, offer a better quality of life, and prolong life,” says consultant vascular and interventional radiologist Dr Alex Tang.

When a patient’s cancer or tumour in the liver cannot be removed by surgery, here are a few options their doctors can offer.

“These treatment options are very effective in treating focal malignant and benign diseases,” says Dr Tang. However, they are often carried out together with ongoing systemic chemotherapy for optimal clinical care.

While these brief descriptions provide a general overview of the treatment options, it is best to consult your attending doctor, oncologist, or interventional radiologist before deciding on treatment strategies.


Percutaneous Ethanol Injection

Dr Tang explains the various
treatment options for liver cancer.

While ethanol is the chemical compound we are drinking when we down that beer, high concentrations of it can kill our cells. In this procedure, interventional radiologists locate the cancers or tumours in their patients with the help of an ultrasound or CT image and inject pure alcohol into them with a very thin needle.

Radio Frequency Ablation (RFA), Microwave, High Intensity Focused Ultrasound (HIFU), Cryotherapy

Besides “poisoning” cancer cells, interventional radiologists can also burn or freeze cancer cells.

In RFA, interventional radiologists locate the cancers or tumours in their patients with the help of an ultrasound or CT image and heat up the needle tip (with radiowaves) to “burn off” the cancer cells. The microwave technique follows the same principle, but as its name indicates, the needle tip is heated up with electromagnetic waves (microwave).

HIFU is a non-invasive procedure that uses a focusing lens to concentrate sound wave energy and burns the tumour cells through the skin.

In cryotherapy, the doctors freeze and kill cancer cells using very low temperatures by injecting inert chemicals (chemicals that do not react with our cells) into them with a needle. Chemicals that are used for this purpose are often liquid nitrogen (-196 degrees Celcius) or argon (-185 degrees Celcius).

Transarterial chemoembolisation (TACE), Radioembolisation with Selective Internal Radiation Therapy (SIRT), Portal vein embolisation

As cancer cells also need oxygen and nutrients to live, they need blood supply to continue to live and multiply. Therefore, one of the ways of killing them is cutting off their blood supply. In TACE, interventional radiologists will locate the arteries that supply the tumour by doing a hepatic angiogram (a special x-ray of the arteries) and infuse anti-cancer drugs through them. Sometimes, they may choose to infuse special plastic beads that are coated with anti-cancer drugs (called DC beads) so that the drugs can be released into the cancer cells over time.

Portal vein embolisation is often done when a patient is suitable for surgery, but the remaining liver cells may not be enough to work properly on their own. By cutting off a branch of portal vein that supplies the segment of the liver that contains the tumour, it can shrink it down and allow the other segments (with normal cells) to grow larger.

This may allow surgeons to reduce their patients’ risk of liver failure when they remove the affected part of the liver.

Sorafenib

Sorafenib is an oral anti-cancer drug that is usually prescribed for patients with advanced and terminal kidney and liver cancer. Patients who are prescribed this drug usually have to take them until they no longer work or have intolerable side effects.

All the above treatments are available in Malaysia except HIFU.


http://thestar.com.my/health/story.asp?file=/2011/9/25/health/9507059&sec=health