Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.

Voltaire


Voltaire was probably correct about the doctors of the eighteenth century. Today, however, doctors know much more about human beings. They know an increasing amount about the diseases they treat, but they are still trying to learn how the medicines work. The literature of today’s medicine often arrogates more than we actually know. New drugs are said to be “targeted” and our interventions are claimed to be “evidence-based” rather than empirical. Yet, as a practical matter, we still do not fully understand how many of the drugs produce therapeutic benefit even when they were “rationally” designed. Nevertheless, therapeutic progress is real and substantial in a number of diseases.
This issue of Hot Topics in Oncology is devoted to hepatocellular carcinoma (HCC), one of the most common malignancies in the world. Though liver cancer was diagnosed in about 21,370 people in the United States in 2008, the incidence worldwide is much higher. This is in part due to the prevalence in some geographic areas of various forms of hepatitis that can lead to HCC and in part due to ethnic differences in disease susceptibility. For example, compared with Caucasians, Hispanics have about three times and Asians nearly five times the incidence of HCC.
Thirty years ago when I was an internal medicine resident, I had a patient who I shall call Avery, a young man who had served in Viet Nam 10 years earlier and who had brought home a serious drug addiction and a case of hepatitis B. The hepatitis progressed to cirrhosis and then to HCC. When I first saw him he was as yellow as a duck’s foot (the phrase of one of my professors). This was meant to imply a deep yellow-orange color associated with serious biliary obstruction of long-standing, as distinguished from the lemon yellow jaundice associated with certain chronic hemolytic anemias. He had tense ascites that restricted his breathing, and his liver was palpable to the pelvis with distinct nodules, large and small.
Thirty years ago, I had little to offer him except pain relief, the intermittent tapping of enough ascites to allow him to breathe, and compassion. When he died, I thought of him as having given his country what Lincoln called “the last full measure of devotion,” even though his death was not directly from a battle wound.
The path he traveled need not be traveled today. With new vaccines and drugs, his prognosis did not have to be bleak. New imaging methods and serum tumor markers detect the progression to hepatic neoplasia earlier in the disease course, and surgical techniques, including resection and transplantation, address the hepatic primary. A variety of local and regional interventions such as chemoembolization, percutaneous ethanol injection, and radiofrequency ablation kill the tumor or arrest its growth. And more recently, even certain drugs can cause the tumor to regress.
The key to managing patients with HCC is to define the status of the underlying liver disease and the stage of the cancer and to choose an intervention that affords the best chance of recovery. In this issue of Hot Topics in Oncology, the management of cirrhosis and its complications (ascites, hepatic encephalopathy, variceal bleeding, etc) is reviewed by Luigi Bolondi and Alice Gianstefani from Bologna. They also discuss in detail a variety of clinical approaches that define the prognosis of patients with distinct manifestations of disease. Staging of liver disease is an evolving art and is crucial to selecting the most appropriate intervention that has the greatest chance of success.
Then Bruno Daniele from Benevento and Massimo Di Maio from Naples discuss in detail patient and disease features that favor the selection of one treatment modality over another. They also discuss exciting new findings that have provided encouragement that drug therapy may become a useful component of treatment. The antitumor effects of sorafenib have exceeded even optimistic expectations, though the duration of benefit remains disappointingly short-lived.
The syntheses that these authors provide are elegant and state-of-the art. The presented information will be of use to every physician who manages patients with compromised hepatic function and will be of special utility in understanding the great strides that have been made in HCC treatment.