With liver cancer, size matters less


FOLLOWING the successful removal of a tumour from his liver, Mr Dominic Foo and his family couldn’t have been happier.

But just a year later, two more tumours were found.

They were larger than the first, but more worrying was their location – near a main blood vessel – which meant surgery might not be an option.

AGGRESSIVENESS PLAYS LARGER ROLE: With liver cancer, the aggressiveness of the tumour - not merely the size - plays a larger role in determining whether a patient is at risk of having a recurrence.

Mr Foo, who thought earlier that he had a good chance of survival – given the small size of his first tumour – now fretted that time was running out and that he might live, at best, another eight months, not the minimum five years that patients with small tumours typically do.

Mr Foo’s earlier sense of optimism wasn’t entirely misplaced.

It was generally believed that the smaller and fewer the tumours, the better the chances of survival following surgery – assuming the cancer had not already spread to other organs.

But a recent study now shows that other factors, notably the natural aggressiveness of the tumour, play a more important role in determining the patient’s chances of survival following surgery, and whether the cancer will return.

“The size factor is true to some extent because if it’s bigger and there are more than one, it implies it has been detected at a later stage,” said Professor Pierce Chow, Senior Consultant, Department of General Surgery, Singapore General Hospital (SGH).

“But in some patients, although the tumour is small, we see features under themicroscope which indicate that it is biologically a very aggressive type of tumour.”

The study, which resulted in this important discovery, was carried out by Dr Lim Kheng Choon, SingHealth Resident, Diagnostic Radiology Programme, SingHealth Residency, who did the research under Prof Chow’s supervision when he was a student at Duke- NUS Graduate Medical School.

“While it has always been known that other factors such as the age of the patient, his relative general health, the functioning capacity of the remaining liver and the aggressiveness of the tumour played a part (in determining how well the patient would do and whether the cancer would recur), which factor was more important, and to what extent, were still being debated,” said Dr Lim.

Prof Pierce Chow

This study demonstrated that one crucial feature to look out for is microvascular invasion, which means the cancer has already begun to invade the small blood vessels.

To determine if the tumour cells have penetrated the small blood vessels, a pathologist has to examine the whole tumour, as microvascular invasion cannot be seen on a scan or detected through a core biopsy.

The study also highlighted a certain pattern in the recurrence rates of the cancer.

Patients with the aggressive form of the cancer, where microvascular invasion was inherent in the tumour, have a higher risk of getting another tumour in the liver.

From the study, “we now know that post-surgery, some patients will inherently do better than others.

Those with higher chances of recurrence will need additional treatment.

It is definitely something we need to look at in the future, based on data provided by this study,” said Prof Chow, Dr Lim’s mentor in the study.

The findings have changed the way Prof Chow follows up on his patients.

“In the past, after resection, patients come back every six months for an ultrasound and blood test in order to catch any new tumours.

But looking at the data on early recurrence in patients with microvascular invasion, I have changed that – I will schedule followup and surveillance every three months for the first two years for these patients.”

By doing this, the cancer can be detected early and some form of treatment can be offered before it’s too late.

“Patients who show no symptoms when their cancer or cancer recurrence is detected stand the best chance of early treatment and good survival,” added Dr Lim.

Prof Chow and Dr Lim encourage regular screening for liver cancer patients, as well as those most at risk of getting the disease such as hepatitis B carriers.

“Asia has a high incidence of hepatitis B, unlike the West.

Liver cancer is therefore a very important cancer here.

If you are a hepatitis B (or C carrier), we recommend you go for screening every six months.

If you don’t know your hepatitis status, it is time to have it checked,” said Prof Chow.

Mr Foo isn’t a real person, but could be any one of the hundreds of people (both men and women) who are diagnosed with the disease every year.

Liver cancer was the fourth most common cancer among men from 2005 to 2009, according to Singapore Cancer Registry statistics.

During this period, liver cancer was the third highest cause of cancer deaths among men, and fifth among women, although it didn’t come in among the most common cancers.

Fortunately, for patients like Mr Foo, new effective therapies are emerging.

Treatment can include selective internal radiation using a chemical element known as yttrium-90 to reduce the size of the tumours, followed by radio-frequency ablation – a minimally invasive procedure that uses radiofrequency energy to burn tumours.

Published in the highly respected international publication, Annals of Surgery, in July this year, the study was authored by Dr Lim Kheng Choon, the top student of the pioneer batch of Duke-NUS Graduate Medical School graduates.

With Prof Chow as his mentor, Dr Lim worked on the study during his research year at Duke- NUS Graduate Medical School.

He built up a database of more than 500 patients from SG H, and detailed analysis found that patients with microvascular invasion fared far worse, surviving an average of three years after surgery compared with almost eight years in those without microvascular invasion.

“We also noted than in the absence of microvascular invasion, size matters very little.

But when there is microvascular invasion, then those with a larger tumour or more tumours did not do so well,” said Dr Lim, who like most in his cohort, held a first degree in a non-related field.

Dr Lim studied mechanical engineering and spent seven years in the air force as an engineer before entering Duke-NUS, which took in its first batch of students in 2007 to turn them into doctors-scientists.

This is the first study to have compared size and number of tumours against microvascular invasion and shown, in a very robust manner, the greater importance of the latter.

It has also opened up new possibilities.

“In future, maybe we might be able to identify a biomedical marker for microvascular invasion, now that we know what to look for.

That way we can identify patients with microvascular invasion presurgically,” said Prof Chow.

Hepatitis B – What you need to know

It is the most common infection of the liver in the Asia-Pacific including Singapore Asia holds more than half the world’s hepatitis B burden.

It is caused by the hepatitis B virus by direct contact with the blood or body fluids of an infected person, such as from mother to child during childbirth, through unprotected sex and sharing of needles.

What is its link to liver cancer?

Hepatitis B is the most common cause of liver cancer worldwide Those who are hepatitis B carriers are 100 times more likely to develop liver cancer than noncarriers More men tend to develop liver cancer than women Depending on the stage that liver cancer is diagnosed, and if left untreated, the average life expectancy is about three to eight months.

Individuals who don’t have hepatitis B can get liver cancer from a hepatitis C infection, cirrhosis arising from chronic alcohol consumption or a fatty liver.

How can hepatitis B be prevented?

Have a three-dose vaccination if you are not naturally immune to the virus.

Have protected sex and avoid multiple partners.

Avoid the sharing of needles, razors and other sharp implements.

Don’t all children get vaccinated against it?

Hepatitis B vaccination has been a part of a national childhood immunisation programme since 1985.

Those born before 1985 were not vaccinated for hepatitis B, but they can check if they have the virus by having a blood test at a hospital, government polyclinic or with a general practitioner.

The test costs between S$30 and S$40 at neighbourhood clinics.

What’s next after blood test results?

If found to be hepatitis Bpositive, a half-yearly screening for liver cancer is recommended If the patient has no history of blood transfusion or doesn’t belong to any high- risk groups, but is tested positive, family members should be informed and tested.

If the test is negative for hepatitis B, vaccination is recommended.

This story was first published in Singapore Health, Sep/Oct 2011.