The emergence of a new discipline, hepatobiliary oncology
Authors: Gregory J. Gores
Journal: Hepatology (2008)

Hepatology is a thriving discipline! There is considerable evidence to support this statement. For example, attendance at National and International meetings sets new records on an annual basis, successful therapeutic options for viral hepatitis are now a reality and liver transplantation is widely established as a life-prolonging procedure for patients with end-stage liver disease. HEPATOLOGY, the official journal of the American Association for the Study of Liver Diseases, has been an objective and prestigious forum for the communication of these advances and its impact factor has benefited. The impact of hepatology as a discipline worldwide relates to the richness and diversity of focused academic niches and special interest groups within our larger professional umbrella. Networks of highly focused specialists have pioneered studies examining therapeutic options for patients with viral hepatitis and gastrointestinal bleeding related to portal hypertension. Many patients with hepatitis C are now essentially cured of this affliction and prophylaxis for variceal bleeding can be regarded as a quality health measure. The success of hepatology is in large part related to the collective labor of these academic professionals. Another disease process affecting the hepatobiliary system, primary malignancies of the liver and bile duct have received less attention. Although a few hepatologists have examined the benefit of surveillance programs for hepatocellular carcinoma and the therapeutic benefit of locoregional therapies, hepatologists have not embraced primary liver cancer with the same organized effort afforded viral hepatitis, portal hypertension and liver transplantation. Studies on liver cell cancer have independently been executed by surgeons, transplant teams, interventional radiologists, hepatologists and oncologists. There has been a lack of standardization in these studies, variable endpoints have been employed and conclusions conflicting. Information has also been limited by the small number of patients studied. Even in such a well-organized effort as liver transplantation, there are no randomized controlled trials systematically evaluating the benefit of treating liver cell cancer in patients awaiting liver transplantation; a cohort of patients taken care of almost exclusively by hepatologists. What accounts for the lack of hepatologists focusing their career on hepatobiliary oncology? It is not the lack of patients, as unfortunately, these diseases are increasing in Western countries.1, 2 Rather it reflects two realities: (1) the lack of organized, multidisciplinary professional structures to encourage networking, share information and promote multi-institutional studies; and (2) the lack of resources to promote such interactions. The incidence of hepatocellular cancer, gall bladder cancer and cholangiocarcinoma combined fall well below common cancers such as colorectal cancer, prostate cancer, lung cancer and breast cancer. The relatively low incidence of hepatobiliary cancers has often made them orphans in regards to federal and/or industrial support. This observation highlights the growing concern that the profit-driven medical:industrial complex is determining in which diseases advances will occur. What can be done to correct this unmet, professional and clinical need — the development of hepatobiliary oncology? Professional associations are needed to foster interest, promote academic initiatives and advocate for our patients afflicted with primary hepatobiliary cancer. The recent formation of a Hepatobiliary Neoplasia Special Interest Group within the AASLD represents such an initiative. The multidisciplinary, newly formed, International Liver Cancer Association (ILCA) also is a step toward addressing this issue. The ILCA's efforts do not represent fragmentation of our umbrella hepatology professional societies, but rather they address an unmet need. The ILCA is analogous to the formation of transplant associations which have over time strengthened rather than detracted from hepatology associations. Special interest groups are vehicles to help drive professional advances. Many of us employ multiple motor vehicles in our daily lives. At times we ride a public bus which carries individuals to multiple destinations (a large society comprised of individuals with diverse professional objectives) and at other times a smaller vehicle with a single destination (a specialized interest group or society in this analogy). We need to support and encourage these efforts to focus attention on hepatobiliary cancers. The second challenge, funding, is more formidable. Currently, the National Institutes of Health (NIH) budget is at best, flat, hindering the allocation of resources for new initiatives and expenditures. On a more promising perspective, the advent of targeted therapies may help re-focus attention on hepatobiliary malignancies. Oncology-based research is now identifying the specific molecular pathways driving cancer proliferation, avoidance of apoptosis, and tumor propagation via angiogenesis. These pathways can be specifically targeted by monoclonal antibodies and small molecules permitting therapeutic precision thereby maximizing therapy and minimizing toxicity.3 Moreover, the uniqueness of a patients' cancer can be identified making customized therapy or personalized medicine a reality. Targeted therapies with biologic or small molecules to disrupt or inhibit major pathways of oncogenesis have now been applied to hepatocellular cancer. The Sorafenib HCC Assessment Randomized Protocol (SHARP) trial has demonstrated the success of this strategy and the success of other agents can be anticipated. The advent of targeted therapies is paradigm changing. We now need specialists focused on hepatobiliary cancer to administer these therapies. Why should hepatologists become involved in hepatobiliary oncology? The answers to this question are intuitive. Most hepatobiliary cancers occur in the background of chronic hepatobiliary diseases; for example, the high risk for developing HCC in patients with cirrhotic stage hepatitis C. Hepatologists see and screen these patients for cancer. Not only does liver disease predispose to cancer, but it complicates treatment of the cancer. At every turn of therapy, the question arises — what is the impact of this disease and therapy on the underlying liver disease? For example, the potential impact of anti-angiogenic therapy on portal hypertension requires thought and attention. Finally, hepatologists are both the primary care and specialist physician for patients with liver disease; to simply turnover such patients to the care of other professionals is not optimal for the patient. These patients require care for their portal hypertension, propensity to retain sodium and water, management of their neoplastic biliary obstruction, etc. This care is best delivered by a hepatologist, in my opinion. Develop multidisciplinary hepatobiliary neoplasia clinics in our Institution Support professional networks and associations focused on hepatobiliary neoplasia Consider the implementation of cross-training programs: oncology fellowship for hepatologists and hepatobiliary fellowships for oncologists Encourage hepatobiliary neoplasia as an academic niche for junior hepatologists Help establish and participate in multi-institutional treatment networks to support therapeutic studies for this disease Encourage basic and translational research in hepatobiliary neoplasia As for the journal HEPATOLOGY, we aspire to become the worldwide forum for high quality, basic, translational and clinical research in hepatobiliary neoplasia. To help accomplish this mission, we will continue to solicit reviews on hepatic oncology, targeted therapies, updates on trial design and clinical reviews on emerging therapies. This journal will serve as a spot-light for the emerging discipline of hepatobiliary oncology.