Jaundice is an uncommon complaint in adults which may potentially signify serious disease. Progressive painless jaundice (as encountered here) is particularly ominous, given its classical association with malignancy; key etiologies to keep in mind include carcinoma of the ampulla of vater, extrahepatic cholangiocarcinoma, and adenocarcinoma of the pancreatic head. That said, it should also be appreciated that painless jaundice is also the most common presentation associated with a resectable and curable malignancy; moreover, it does not always imply malignancy, as certain benign diseases (such as autoimmune hepatitis) may also present in this fashion. The remainder of the history and examination does not provide clues towards a likely causative etiology; the next step should be properly targeted investigations, starting with a liver profile and imaging of the liver and biliary tree. The liver profile reveals the presence of direct hyperbilirubinemia along with elevated alkaline phosphatase (ALP) and gamma-glutamyl-peptidase (GGT) levels, i.e. a cholestatic picture. Note that ALP levels are more than thrice the upper limit of normal; this degree of elevation is more in favor of an obstructive cause. This is supported by the normal transaminase (i.e. ALT/AST) levels; these are markers of liver injury, and in patients with hepatocellular disease, one would typically expect some degree of elevation. Ultrasound is the initial imaging modality of choice in patients with cholestatic jaundice; the key observation to be made is the presence or absence of biliary duct dilation. In this patient, sonography reveals dilation of the intrahepatic bile ducts, along with a normal common bile duct and collapsed gallbladder; note that this hints at an obstruction of the proximal extrahepatic biliary tree. Further imaging of the biliary tract and surrounding structures is a must; magnetic resonance imaging (MRI) of the abdomen in conjunction with magnetic resonance cholangiopancreatography (MRCP) is a good choice in this regard. The MRI/MRCP findings in turn reveal a stenotic lesion at the confluence of the right and left hepatic ducts (i.e. the hilar region), with imaging characteristics suggestive of a cholangiocarcinoma. Thus the probable diagnosis is a Bismuth-Corlette type 2 Hilar Cholangiocarcinoma (Klatskin tumor). Unfortunately, the MRI also demonstrates tumor metastasis to the lymph nodes surrounding the pancreas; thus, this tumor is no longer resectable. Endoscopic retrograde cholangiopancreatography (ERCP) with stenting is not preferred in patients with hilar cholangiocarcinoma, as there there is high morbidity (particularly sepsis) and procedure related mortality, along with a low successful drainage rate. Symptomatic relief of the pruritus will improve his quality of life. Vitamin K is not currently indicated, as his INR is normal. Note that a chest x-ray should be performed to exclude pulmonary metastasis.
While cholangiocarcinomas can occur anywhere in the biliary tract, the hepatic duct bifurcation is the most frequently involved site, accounting for approximately 60% to 80% of cases. These hilar cholangiocarcinomas are also known as Klatskin tumors; they were first identified by Gerald Klatskin in 1965. Klatskin tumours are typically small, poorly differentiated, and aggressive in nature; they tend to obstruct the intrahepatic biliary tree. Similar to other forms of cholangiocarcinoma, their exact etiology is unclear, although it is known that conditions giving rise to acute or chronic biliary tract epithelial injury may predispose to malignant change. Key predisposing conditions include primary sclerosing cholangitis, congenital biliary cystic diseases (such as choledochal cysts or Caroli's disease), and chronic biliary tract parasitic infections. Klatskin tumors have traditionally been classified into 4 types (ranging from I-IV) via the Bismuth-Corlette classification: Type I - tumor below the hepatic confluence Type II - involvement of the confluence Type IIIa / IIIb - involvement of the confluence and right (IIIa) or left (IIIb) lobe Type IV - tumor in both hepatic lobes, or multicentric tumor Painless jaundice is the predominant presenting complaint in almost all cases of Klatskin tumor; non-specific complaints (such as weight loss, abdominal pain, and pruritus) may also be present. Note that cholangitis is uncommon. The laboratory findings in these patients typically suggest a cholestatic pattern, with increased direct bilirubin, increased alkaline phosphatase (ALP) and elevated gamma-glutamyl-peptidase (GGT). In certain patients, CA 19-9 levels and/or carcinoembryonic antigen (CEA) levels may be elevated; however, it is important to note that neither of these tumor markers are specific to the disease. Abdominal ultrasound should be the initial imaging study in these patients; this will typically show a dilated intrahepatic biliary tree, a normal or collapsed gallbladder and extrahepatic biliary tree, and a normal pancreas. Magnetic resonance imaging (MRI) combined with magnetic resonance cholangiopancreatography (MRCP) is the current gold standard for imaging hilar lesions. The presence of bilobar ductal dilation with a contracted gallbladder or disjunction of the hepatic lobes, with or without thickening in the MRCP suggests a Klatskin tumor; MRI typically shows a hilar mass which is hypointense in T1-weighted images, and hyperintense in T2-weighted images. Computerized tomography (CT) is an alternative modality of imaging; three phase helical CT scans allow good discrimination of intrahepatic biliary stenoses, and also allow visualization of hilar lymph nodes. Endoscopic retrograde cholangiopancreatography (ERCP) is less prefered now, owing to the increased risk of biliary tract sepsis in patients with cholangiocarcinoma. However, note that many surgeons still prefer images from endoscopic or percutaneous cholangiography over MRIs for defining the extent of surgery. Positron emission tomography (PET) can also visualize cholangiocarcinomas (due to their high glucose uptake), and are capable of detecting even small lesions. However, they are primarily used for detecting hidden metastases. Obtaining a preoperative histological diagnosis of a Klatskin tumour is difficult; it is not essential for surgical intervention. Imaging findings of extrahepatic disease, bilobar liver metastases, or involvement of the major hepatic portal vessels preclude curative resection; the cholangiographic appearance of extensive bilobar proximal extension into the hepatic parenchyma also indicates unresectability. That said, it is important to appreciate that the (imaging) stage of the tumor and patient's fitness for surgery are not the only factors which determine resectability; the level of experience of the operator also plays a major role. Additionally, even with current highly accurate imaging methods, definitive assessment of resectability may still require laparotomy in many patients. Palliation is indicated in patients with unresectable Klatskin tumours or in patients not fit for surgery. Percutaneous transhepatic catheters give the best access for palliation and avoid the complications of recurrent cholangitis and/or liver abscess formation. However, these patients may still experience biliary sepsis, catheter occlusion or sludge formation. Note that endoscopically-placed biliary catheters are not preferred for Klatskin tumours. Other options for palliation include bypass surgery, photodynamic therapy, intraluminal brachytherapy, and external radiation and systemic therapy. The Mayo Clinic has developed a novel therapeutic protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation for patients with unresectable tumors; this has displayed excellent survival rates, and is increasingly entering widespread practice. Overall, Klatskin tumors have a poor prognosis; statistics from the National Cancer Institute (NCI) give a 5-year survival rate of 30% for localized disease; 24% for regional disease; and only 2% for disease with distant spread.