Recently at the delicatessen counter of a supermarket, I heard a mother asked her teenage son “Would you like some salami for lunch?”. After receiving an affirmative reply the mother promptly asked for 20 slices of salami. The teenage boy was shorter than me but he was 3 times as broad and deep as me! In other words, he was overweight, if not obese, with a sizeable belly.

Obesity has reached an epidemic proportion worldwide and the incidence of metabolic syndrome (MetS) seems to be paralleling obesity. Metabolic syndrome is strongly linked to insulin resistance, abdominal obesity, diabetes mellitus and dyslipidaemia. The adipose tissue (or more commonly known as fat) in the body can be divided into subcutaneous adipose tissue and visceral adipose tissue (VAT). Overweight and obese people have increased amount of VAT. One of the many sites for VAT accumulation is the liver and this can give rise to a condition called nonalcoholic fatty liver disease (NAFLD). When inflammation sets in, the condition is called nonalcoholic steatohepatits (NASH). If left unchecked, NASH can lead to progressive liver fibrosis and eventual liver cirrhosis. There is increasing evidence that people with visceral fat accumulation have an increased risk of developing primary liver cancer or hepatocellular carcinoma (HCC). Will visceral fat accumulation cause increased risk of HCC recurrence after curative treatment in patients with suspected NASH?

Researchers from the University of Tokyo studied 62 patients with HCC on a background of suspected NASH (Gut 2009; 58: 839 – 844). The visceral fat area (VFA) was determined by CT images at the time of HCC diagnosis. The patients were divided into two groups based on the VFA:- high VFA group (VFA > 130 sq. cm in males, > 90 sq. cm in females) and control group (VFA < 130 sq. cm in males and < 90 sq. cm in females). Using percutaneous radiofrequency ablation, all patients were treated with a curative intent between 1999 and 2006. These patients were followed up until HCC recurrence. The cumulative recurrence rates at 1, 2 and 3 years in the VFA group were 15.9%, 56.5% and 75.1% , respectively. These are significantly higher values than those found in the controls, being 9.7%, 31.1% and 43.1%, respectively.  The researchers concluded that visceral fat accumulation is an independent risk factor for HCC recurrence after curative treatment in patients with suspected NASH.

While I applaud the mother who wanted to look after her child well, perhaps she has been looking after him far too well for his own good. Saddling an adolescent with excess / excessive weight is equivalent to storing up future health problems for the child. When he / she attains adulthood and starts developing diabetes mellitus, arthritis in the hips and knees, he / she might think differently about the excessive amount of food you have been feeding him / her.

As 2008 draws to a close, most, if not everyone, will be glad to see the end of 2008 and look forward to a hopefully better 2009 and calmer financial clime. For those of us who treat patients with cancer, every year we always hope for something better to come along for our patients. The recent editorial, by Drs Kelly and Venook of the University of California, in the Journal of Clinical Oncology commented on the recent availability of sorafenib (Nexavar) for the treatment of patients with advanced hepatocellular carcinoma (HCC) and how sorafenib has ‘ushered in an era of hope for patients with HCC’ (J Clin Oncol 2008; 26: 5845 – 5848).

The study showing sorafenib was effective in treating patients with advanced liver cancer was the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) study. The data was first reported at the American Society of Clinical Oncology (ASCO) meeting in June 2007. On the basis of these results, the drug was approved in both Europe and the United States a few months later. The SHARP study involved 602 patients, 20% positive for hepatitis B and 30% for hepatitis C. It showed that sorafenib prolonged overall survival to 10.7 months vs 7.9 months on placebo treatment (N Engl J Med 2008; 359: 378 – 390). Corroborating but different results have since been reported from an Asian trial involving 226 patients in which > 70% of them were positive for hepatitis B. The Asian trial showed that patients on sorafenib survived 6.2 months while those on placebo only survived 4.1 months (Lancet Oncol, published online 16/12/2008).

Drs Kelly and Venook wrote “This study (SHARP study) offers the first hope for life prolongation for more than 600,000 patients who die each year from HCC worldwide. With the first hope of an active therapy in a grim disease, there is a natural tendency toward expansiveness – the hype.” They say that clinicians need to question whether the patients who took part in the trial are similar to the patients they see in their office and how far the results can be generalized.

Since sorafenib was made available to all in the second half of 2007, I have, on multiple occasions, encountered patients who refused other forms of treatment and insisted on taking sorafenib alone because they heard or were told that sorafenib is effective against HCC. Unfortunately, the exact role for sorafenib in the management algorithm of HCC has not been defined yet. The data so far tells us that sorafenib, when compared to no treatment at all, can prolong life in patients with advanced HCC and good underlying liver function. It certainly has not been shown to cure patients or prolong life significantly in those with less advanced disease. In the world of finance, if you fall for the ‘hype’ around a bad financial product, you are likely to lose money. If you fall for the ‘hype’ around a new medicine, you are likely to lose more than just money.

Sorafenib has certainly given hope to patients with advanced HCC. Now there are many ongoing studies looking at how to combine sorafenib with other agents in treating other HCC patients. Lets hope these studies will bring better news to our patients in 2009. Happy New Year!