Portal vein encasement complicates resection of Klatskin's tumor in the liver

■ Cholangiocarcinoma is a rare disease but has an increased incidence in patients with underlying sclerosing cholangitis or choledochal cysts.

■ Perihilar cholangiocarcinoma, also called Klatskin's tumor, is the most common. Klatskin's tumors are classified with the Bismuth-Corlette system.

■ Surgical resection is the only curative treatment for cholangiocarcinoma. Resectability is largely determined by the extent of ductal and vascular involvement.

■ Patients have a better than 5-year survival rate when an R0 resection is obtained.

CASE

A 65-year-old white man presented to his primary care physician (PCP) complaining of pruritus, jaundice, and a 2-month history of dark urine. He also admitted to an unintentional 10-lb weight loss in 2 months, anorexia, and epigastric fullness after meals. He denied fever, sweats/chills, abdominal pain, nausea, vomiting, change in bowel or bladder habits, chest pain, shortness of breath, and headaches.

The patient's medical and surgical histories were unremarkable; he had no prior hospitalizations; and he had no significant family history. He denied alcohol, tobacco, and illicit drug use. His medications included oral ciprofloxacin, 750 mg three times a day, for 1 month to treat a biliary tract infection. The patient had no known drug allergies.

The PCP ordered CT, which revealed an ill-defined mass measuring 2.1 × 2.8 × 2.6 cm at the level of the right hepatic duct with intrahepatic ductal dilatation and encasement of the right portal vein immediately beyond the main portal vein bifurcation (Figure 1). The patient subsequently underwent endoscopic retrograde cholangiopancreatography (ERCP) with placement of a common bile duct stent. Following the stent placement, the patient's total bilirubin level normalized and his jaundice resolved. The patient was then referred for surgical evaluation.

Presurgical physical examination The patient was in no acute distress. Vitals signs were temperature, 98.8°F; pulse, 62 beats per minute; BP, 112/60 mm Hg; respirations, 16 breaths per minute. Jaundice of the skin was apparent. There was slight scleralicterus. His abdomen was soft, nondistended, and nontender to palpation. There was no abdominal organomegaly or guarding. No Murphy's sign was noted. Heart rate and rhythm were regular with audible S₁ and S₂. Lungs were clear to auscultation in all fields, bilaterally. All other physical examination findings were unremarkable.

Pertinent laboratory studies, including liver function enzymes, and an MRI/magnetic resonance cholangiopancreatography (MRCP) were ordered. Laboratory test results were total bilirubin, 6.8 μmol/L; AST, 157 U/L; ALT, 166 U/L; alkaline phosphatase, 271 U/L. MRI revealed a 1.9 × 1.6-cm hyperintense T2 lesion with delayed enhancement in the region of porta hepatis with intrahepatic ductal dilatation. Further cross-sectional imaging revealed encasement of the right portal vein. MRCP revealed a perihilar mass. Based on imaging studies, type IIIa Klatskin's tumor with ipsilateral right portal vein encasement was the suspected diagnosis.

Treatment The patient was admitted to the surgical service. Despite the biliary stent, the patient had persistent intra-hepatic ductal dilation and hyperbilirubinemia. Percutaneous transhepatic cholangiography (PTC) was performed, and a percutaneous catheter was placed to more adequately drain the biliary system and correct the patient's bilirubin level before surgery (Figure 2).

Cross-sectional imaging and the cholangiogram indicated that the tumor was resectable because it involved only the right hepatic biliary ducts (type IIIa); and although vascular extension of the tumor was present, it only involved the ipsilateral branch of the right portal vein. An extended right hemihepatectomy (removal of liver segments IV, V, VI, VII, and VIII) would be required to extirpate all the disease; therefore, preoperative liver volumetrics were obtained to ensure that the future liver remnant (segments I, II, and III) would be of adequate volume to avoid postoperative liver insufficiency. Volumetrics revealed that the remnant encompassed 34% of the entire liver volume and was deemed to be adequate. The patient was taken to the operating room after confirming normalization of the bilirubin level.

At surgery, it became evident that the tumor involved not only the biliary confluence and right hepatic ducts, but also part of the left hepatic duct. An extended right hemihepatectomy with en bloc resection of the extrahepatic biliary tree was performed. Dissection of the left hepatic duct was taken up to the base of the umbilical fissure (the margin was noted to be negative). In addition, the right portal vein was found to be completely involved with the tumor. Specifically, it was involved down to the level of the bifurcation of the main portal vein. Given this, the right portal vein and the main portal vein confluence were resected. The left portal vein was then anastomosed primarily to the main portal vein to reconstruct the portal vein anatomy.

Outcome On final surgical pathology, the tumor was noted to be a 4-cm cholangiocarcinoma that invaded the liver with no associated nodal metastases (T3N0). The surgical margins were uninvolved. The patient's postoperative course was noteworthy for a perihepatic fluid collection that was managed with percutaneous drainage. He was discharged home on postoperative day 7. The percutaneous drain was removed at his first postoperative clinic appointment. The patient is alive and disease-free at 12 months after surgery.

DISCUSSION

Cholangiocarcinoma is an uncommon malignancy. It accounts for 3% of all malignancies, with more than 5,000 new cases diagnosed each year. Males are affected slightly more often than females (a 1.3:1.0 ratio in favor of men), and peak incidence is in the fifth to seventh decade of life.¹ Risk factors include sclerosing cholangitis (8%-20% lifetime risk), choledochal cysts (3%-28% lifetime risk),¹ ulcerative colitis, biliary stone disease, certain chemical agents, Asian descent, and liver flukes such as Clonorchis sinensis and Opisthorchis viverrini.²

Cholangiocarcinomas are categorized by anatomic location: intrahepatic, perihilar, or distal. Perihilar cholangiocarcinoma is the most common type and accounts for 60% to 70% of all cases.³ Perihilar cholangiocarcinoma is often referred to as Klatskin's tumor, as Gerald Klatskin, MD, was the first to describe this clinic entity in 1965^.4 Perihilar cholangiocarcinomas can be further subclassified, based on the location within the perihilar area, with the Bismuth-Corlette system (Figure 3).

In the Bismuth-Corlette classification schema, type I tumors arise near the biliary confluence without involvement of the left or right biliary ducts and are therefore confined to the common hepatic duct. Type II tumors arise at the biliary confluence with extension to the left and right hepatic ducts. Type IIIa tumors arise at the biliary confluence with extension to the right hepatic duct up to the second order ducts. Type IIIb tumors arise at the biliary confluence with extension to the left hepatic duct up to the second order ducts. Type IV tumors arise at the biliary confluence with bilateral extension to the second order biliary ducts.⁵

A tumor, node, metastasis (TNM) staging system described by the American Joint Committee on Cancer (AJCC) is also used to classify cholangiocarcinoma. In the AJCC classification system, stage IA tumors are limited to the bile duct, stage IB tumors invade periductal tissue, stage IIA tumors are locally advanced without regional lymph node metastases, stage IIB tumors are locally advanced with regional lymph node metastases, stage III tumors are locally advanced and deemed unresectable, and stage IV tumors have distant metastases.⁶

Our patient presented with the most common symptom for cholangiocarcinoma: painless jaundice (90% of patients).⁷ Other nonspecific symptoms may include weight loss, fever, night sweats, anorexia, vague abdominal pain, malaise, and fatigue. With the exception of jaundice, physical examination findings are usually normal.

In addition to routine laboratory tests, the diagnostic work-up involves several imaging modalities (ultrasonography, three-dimensional CT, and MRI) to define the extent of lobar atrophy/hypertrophy, as well as the extent of local vascular involvement. ERCP, MRCP, and PTC are more helpful with defining the anatomical location of the tumor within the perihilar biliary system. Distant metastases are best detected using CT and, occasionally, positron emission tomography.¹ Although no tumor markers are specific to cholangiocarcinoma, serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels may be elevated. Tissue diagnosis can be established via percutaneous fine-needle aspiration, aspiration biopsy, brush and scrape biopsy, or cytologic examination of bile; however, prolonged efforts to establish a tissue diagnosis are not indicated unless the patient is not a candidate for surgery.⁷

The only chance for cure of perihilar cholangiocarcinoma is surgical resection. Tumor-specific relative and absolute contraindications to surgical resection are involvement of bilateral second-order biliary ducts (type IV), involvement of unilateral second-order biliary ducts with contralateral vascular encasement, and bilateral vascular extension or encasement/occlusion of the main portal vein.

Margin-negative (R0) resection at surgery is one of the most reliable predictors of long-term survival. For patients with perihilar cholangiocarcinoma, surgical resection with both an extrahepatic bile duct resection and a concurrent liver resection offers the best chance at obtaining an R0 resection.⁸ Five-year survival following an R0 resection of a perihilar cholangiocarcinoma is 30%. In comparison, 5-year survival following an R0 resection of intrahepatic or distal cholangiocarcinoma is 63% and 27%, respectively.⁵

Unfortunately, up to 50% to 90% of patients with hilar cholangiocarcinoma present with unresectable disease.⁵ Median survival for patients with unresectable intrahepatic and perihilar tumors is 6 to 7 months and 5 to 8 months, respectively.⁷ For patients with unresectable disease, the goal is to alleviate symptoms (pruritus and jaundice) and to prevent complications of obstruction (cholangitis and hepatic failure), which are the most common immediate causes of death.⁶ This is accomplished with drainage of the biliary tree. Drainage may involve ERCP with biliary stent placement; PTC with catheter placement that can be internalized or externalized; and, rarely, operative biliary-enteric bypass. The roles of liver transplantation, radiation therapy, and chemotherapy for patients with cholangiocarcinoma are controversial.⁷

Routine follow-up of a patient after resection is a first postoperative visit 1 to 2 weeks after surgery, and then every 3 to 6 months for at least 5 years. Follow-up studies are aimed at detecting recurrence and include history and physical examination, as well as liver function tests and imaging studies. Risk factors for recurrence are margin-positive resection, lymph node metastases, and vascular involvement.⁹ The most likely sites of recurrence of perihilar tumors after resection are within the bile duct, in the regional lymph nodes, or in the liver.⁶ In these circumstances, treatment is directed at palliation of symptoms as described above. JAAPA

Kathryn Hines works in the Division of Vascular Surgery, Johns Hopkins Hospital, Baltimore, Maryland, and is Director, Advance Surgical Preparedness Program for Physician Assistants, The George Washington University, Washington, DC. Timothy Pawlik is Associate Professor of Surgery and Oncology; Director, Hepatobiliary Surgery Program; and Director, Liver Tumor Center Multidisciplinary Clinic; at Johns Hopkins Hospital, Baltimore, Maryland. The authors have indicated no relationships to disclose relating to the content of this article.

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