The 2009 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Hepatobiliary Cancers (to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org) addresses 4 main tumor groups: hepatocellular cancer, cancer of the gallbladder, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma.
The incidence of hepatocellular cancer seems to be significantly higher in the Middle East and North Africa (MENA) region than in the West. The age-standardized incidence rate is 12.8 per 100,000 population in Egypt,1 8 per 100,000 in Pakistan,2 and 4.2 per 100,000 in Saudi Arabia,3 compared with 2.5 per 100,000 in the United States.4
The region also shares some unique regional risk factors. Hepatitis B and C infections seem to be particularly important. A predominance of hepatitis B virus surface antigen is seen in patients with hepatocellular cancer from most Asian, African, and Latin American countries; hepatitis C predominates in Japan, Pakistan, Mongolia, and Egypt.5
Although the MENA region is not homogeneous, most countries represented in the committee have some common issues, albeit to a variable extent. These include delay in diagnosis, often from an absence of screening programs in those infected with hepatitis B or C, and a shortage of trained staff required for diagnosis and treatment, including gastroenterologists/hepatologists, radiologists, hepatobiliary surgeons, and oncologists. Furthermore, insufficient or, in some cases, nonexistent liver transplant facilities are a serious limitation to treatment for some patients. Pakistan, with a population of more than 170 million, has no liver transplant program. India has 3 centers, performing a total of 550 transplants annually. Egypt has 10 centers, with 150 to 200 transplants performed per year, whereas Saudi Arabia has 3 centers, performing 120 transplants annually.
The costs associated with diagnosis and treatment are an increasing concern in an age of molecular and targeted therapies. Sorafenib for treating hepatocellular carcinoma, for example, is too expensive to be used by most eligible patients in many countries. It is currently recommended primarily in patients with Child's A disease, precluding its use in most patients in the MENA region. Additionally, the modest benefit in survival improvement means that both patients and physicians question the cost/benefit analysis.
Shortage of trained staff is a major problem in many countries in the region. Interventional radiologists are a rare species in many countries. Currently, only 4 centers in Pakistan offer transarterial chemoembolization, with each performing fewer than 500 procedures per year, for an estimated 15,000 new cases per year. A dearth of surgical expertise for liver resection and transplantation exists across the region.
Therefore, numerous challenges exist in the region. A large number of patients have hepatitis B and C infections, suggesting a huge tumor load in the future. Patients present at an advanced stage, with poor background liver function in up to half, thus precluding many treatment options. A culture of cooperation between different specialties is often lacking, with multidisciplinary care the exception rather than the norm. This results in squandering of research opportunities and lack of progress at the local, national, and regional levels.
The following also contributed to the process of guideline formulation and revision, as members of the NCCN–MENA Hepatobiliary Guidelines Review Committee: Khalid Omer Abdullah, King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia; Hassan Jaafar, Tawam Hospital, Al-Ain, United Arab Emirates; Kakil Ibrahim Rasul, Hamad Medical Corporation, Doha, Qatar; Suayib Yalcin, Hacettepe University Institute of Oncology, Ankara, Turkey; and Abdel-Rahman El-Zayadi, Ain Shams University, Cairo, Egypt.
Ibrahim AS. Liver and intrahepatic bile duct cancer. Available at: http://seer.cancer.gov/publications/mecc/mecc_liver.pdf. Accessed March 31, 2010.
Yusuf MA, Badar F, Meerza F et al.. Survival from hepatocellular carcinoma at a cancer hospital in Pakistan. Asian Pac J Cancer Prev 2007;8:272–274.
Kindgom of Saudi Arabia Ministry of Health National Cancer Registry. Cancer incidence report Saudi Arabia 2003. Available at: http://www.kfshrc.edu.sa/oncology/files/NCR2003.pdf. Accessed March 31, 2010.
Raza SA, Clifford GM, Franceschi S. Worldwide variation in the relative importance of hepatitis B and hepatitis C viruses in hepatocellular carcinoma: a systematic review. Br J Cancer 2007;96:1127–1134.
Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer 2006;118:1591–1602.
Khuroo MS, Mahajan R, Zargar SA et al.. Prevalence of biliary tract disease in India: a sonographic study in adult population in Kashmir. Gut 1989;30:201–205.
Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999;30:1434–1440.
Bruix J, Castells A, Bosch J et al.. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 1996;111:1018–1022.
Pawlik TM, Delman KA, Vauthey JN et al.. Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 2005;11:1086–1092.
Llovet JM, Mas X, Aponte JJ et al.. Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut 2002;50:123–128.
Yao FY, Kerlan RK Jr, Hirose R et al.. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 2008;48:819–827.
Takada T, Amano H, Yasuda H et al.. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreatobiliary carcinoma. Cancer 2002;95:1685–1695.