Cholangiocarcinoma (CCA)


Cholangiocarcinoma (CCA) represents a heterogeneous group of adenocarcinomas that form in the biliary tract.1,2 Cholangiocarcinoma is accountable of 3% of all gastrointestinal tumors and is the second most common cancer of the liver.2 Tumors can be classified as intrahepatic (iCCA) and extrahepatic (eCCA), according to their anatomical origin. Extrahepatic CCA can be also distinguished as perihilar (pCCA) and distal (dCCA) tumors.3 In addition to their different location, these tumors have distinct epidemiology, clinical presentation, and prognosis.1,3

The diagnosis of CCA relies on a combination of imaging techniques with the evaluation of tumor markers. These techniques may also require invasive procedures. Tumor confirmation is most often obtained through a biopsy.

Symptoms associated with CCA are typically nonspecific, such as malaise, fatigue, or abdominal pain.5-7 Jaundice may point to a common obstruction of the biliary tract.5 These symptoms are not usually found in early stages of the disease, and when a diagnosis is finally reached, the malignancy has typically progressed to an unresectable state.8

Cholangiocarcinoma can cause a number of complications, including infections that may result in liver failure. Other complications commonly originate from the radiation and surgical treatment undergone by the patients. Medical procedures to alleviate bile buildup in the liver are also associated with several potential complications. 

Infection (Cholangitis) 

Common complications in CCA can derive from the obstruction of the bile ducts. When the bile ducts are blocked because of a tumor, the drainage of bile is compromised. In this situation, the patient can present jaundice but can also develop infection (cholangitis) and liver dysfunction.9,10 Preoperative cholangitis is an important risk factor of liver failure in patients who go through an hepatectomy.10 A biliary drainage may be performed to increase remnant liver function and avoid hepatic failure in patients presenting with obstructive jaundice. A percutaneous transhepatic catheter drainage or the endoscopic placement of a stent can help relieve the biliary obstruction.9 The benefits of each procedure should be, however, carefully assessed, as percutaneous transhepatic drainage may result in further infection and involves a risk of seeding, eventually compromising surgery in patients who do present with resectable tumors.11-13 The use of stents to relieve obstruction has been associated with less complications and with longer survival.14

Cirrhosis

Biliary obstruction caused by a tumor can lead to secondary biliary cirrhosis.15 This complication is, however, more frequently seen as secondary to the diagnosis of primary or secondary sclerosing cholangitis.16

Complications associated with radiation treatment are linked to elevated morbidity and mortality.17 Contemporary stereotactic body radiotherapy in CCA may lead to induced liver dysfunction and biliary strictures and can also damage the gastrointestinal mucosa.18 Endothelial cells from the portal structures are sensitive to radiation; therefore, portal venous and hepatic arterial complications can occur. These complications can be managed by performing an early percutaneous transhepatic portal angioplasty and a stent placement.13

The majority of patients with CCA have an unresectable disease, as they present with locally advanced or metastatic disease. Only about 25% of patients will be candidates for surgery.2 There are, however, many complications to consider after surgery. Postoperative complications are thought to be induce systemic inflammation that negatively affects the immune response developed by the patient to fight a cancer.19,20 Although postoperative morbidity is still high, the improvement of surgical techniques as well as the perioperative management have both contributed to a decrease in postoperative mortality.21 

In CCA, major postoperative complications include intra-abdominal abscesses, sepsis, bile duct leaks, and also biliary fistulae.6,17 Higher rates of these complications are expected when the patient presents uncorrected preoperative jaundice.6 Hepatectomy in pCCA can commonly result in hemorrhage; infection; and hepatic, renal, and cardiorespiratory failure.22 When a patient with pCCA experiences an extended hepatectomy with extrahepatic bile duct and regional lymph nodes resection, a contaminated bile often leads to postoperative cholangitis.10 In experienced medical centers in Europe, the 90-day mortality rate postsurgery can reach 10%. These patients die mostly from liver failure.2 When it is possible to avoid major postoperative complications, the 5-year disease-free and overall survival of patients with iCCA can increase at least 3 times.20 Patients experiencing major complications after surgery might be candidates for adjuvant chemotherapy.20

Venous thromboembolism is also commonly observed in patients with CCA.23 Late vascular complications can occur after living donor liver transplant in patients with pCCA. The risk for vascular complications may increase with the use of neoadjuvant radiation; however, these thrombotic effects do not influence long-term survival.24 Recurrence rates are also significant, which led to liver transplantation being initially contraindicated for the treatment of pCCA.2 The use of neoadjuvant chemotherapy after liver transplantation, however, has been reported to contribute to a 5-year disease-free survival of 65%.2

References

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  23. Jeon HK, Kim DU, Baek DH, et al. Venous thromboembolism in patients with cholangiocarcinoma: focus on risk factors and impact on survival. Eur J Gastroenterol Hepatol. 2012;24(4):444-449. doi:10.1097/MEG.0b013e328350f93c
  24. Tan EK, Rosen CB, Heimbach JK, Gores GJ, Zamora-Valdes D, Taner T. Living donor liver transplantation for perihilar cholangiocarcinoma: outcomes and complications. J Am Coll Surg. 2020;231(1):98-110. doi:10.1016/j.jamcollsurg.2019.12.037

Article reviewed by Harshi Dhingra, MD, on July 1, 2021.