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Located deep within the surgical soul, and surrounded by a forest of critical structures, cancers of the distal biliary tract and periampullary region are difficult to diagnose, and even more difficult to treat. They demonstrate aggressive biology and they present late, features that often make them unmanageable, and even uniformly fatal. However, advances in our understanding of molecular genetics, diagnostic imaging, surgical technique, neoadjuvant and adjuvant therapies, and palliative care have opened new options for the care of patients with these malignancies. Scientific advances over the next few years will place us on an exciting new frontier in the journey to successfully address what has been one of surgery’s greatest challenges.


Each year 13,000 people in the United States are diagnosed with biliary tract cancer, and close to 4000 people die. While these numbers may be small, accounting for only 3% of all gastrointestinal malignancies, the rising incidence, advanced presentations, and high associated mortality of these cancers make their early detection and effective treatment an urgent priority.1

Cholangiocarcinoma (CC) affects a critical and complex anatomic region, and diagnostic and therapeutic approaches must account for the specific anatomic location and context of each case. Indeed, the broad classification of CC reflects essential anatomic considerations. CC is often categorized as intrahepatic cholangiocarcinoma (iCCA) (6% of all CCs), perihilar cholangiocarcinoma (67% of all CCs), and distal cholangiocarcinoma (dCCA) (27% of all CCs). This chapter focuses on malignancies of the dCCAs and cancers of the ampulla (ACs) and adjacent structures. Successful curative and palliative approaches to cancers at this location require detailed insights about histopathology, molecular pathology, anatomy, and surgical technique. dCCAs and ampullary cancers are among the most difficult and most rewarding malignancies to treat.2  


Cholangiocarcinomas arise from the epithelium of the biliary tract and are therefore considered to be adenocarcinomas. Although most CCAs are sporadic with no identifiable risk factors, genetic studies and epidemiological associations suggest an interplay of host factors, inflammation, and the environment in the pathogenesis of CCAs. In the United States, the incidence of CCAs has been reported to range from 2.1 to 3.3 per 100,000, while in Southeast Asia, rates as high as 113 per 100,000 have been reported. This huge discrepancy in incidence has been attributed to differences between populations in risk factors such as hepatobiliary fluke infestation of the bile ducts (Opisthorchis viverrini, Clonorchis sinensis), bile duct cystic disorders, and hepatolithiasis (especially with calcium bilirubinate stones). CCAs have also been associated with inflammation and bile stasis caused by biliary enteric drainage. Thorotrast, an old radiocontrast dye used in the 1930s, and similar agents have been associated with a 300 times increase in the risk of CCA.3

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC), an autoimmune inflammatory condition of the bile ducts that is ...

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