Extrahepatic cholangiocarcinoma (Klatskin tumor)

What is it?

Cholangiocarcinoma is a malignancy that results from a transformation of the cells of the biliary tract, the channels that transport bile from the liver to the intestines, and accounts for about 20% of all primary liver cancers. It affects mostly men and peaks in the seventh decade of life.

The cystic duct from the gallbladder joins the hepatic duct, forming a bile duct which, together with the pancreatic duct, ejects its contents into the intestine (duodenum) through a valve called the Vater ampulla. Cholangiocarcinoma can originate from the epithelial cells of the bile ducts, both intrahepatic and extrahepatic, except for the gallbladder and Vater ampulla.

Depending on their anatomical location in the biliary tree, they can be divided into:

  • Peripheral or intrahepatic (ICC), which occurs within the liver
  • Extrahepatic (CCE), which originates in the extrahepatic biliary tract and, in turn, is divided into:
  • Hilary or Klatzkin tumor, which originates from the junction of the right or left biliary tract (biliary carrefour)
  • Distal, which arises from the terminal part of the biliary tract.

From the histological point of view, that is, from the point of view of characteristics of its constituent cells, cholangiocarcinoma can take different variants: mainly it is an adenocarcinoma (papillary, mucinous, clear cell, intestinal type, etc.) or carcinoma (squamous cell, undifferentiated, small cell, etc.). Depending on the degree of differentiation, i.e., whether the tumor cells resemble the epithelial cells of origin, tumors are divided into well differentiated, moderately differentiated, and poorly differentiated or undifferentiated.

About 50,000 new cases of liver cancer are diagnosed in Europe each year, of which cholangiocarcinoma accounts for about 20%. The annual incidence rate in Europe is about 1.5 cases per 100,000 people. The disease is more common in Southeast Asian countries because of various environmental risk factors, although in recent years the number of new cases has been increasing in the West as well.

Most cholangiocarcinomas occur without obvious causative factors. However, in a minority of cases, conditions, habits, or environmental exposures are known to increase the likelihood of developing cancer. The major identified risk factors, which are united by the chronic inflammatory process of the biliary structures (due to obstruction of the biliary tract) are: primary sclerosing cholangitis; cystic malformations of the biliary tract (Caroli disease and choledochal cysts); parasitic infestations (Clonorchis sinensis, typical of eastern countries); cirrhosis of the liver (often due to alcohol abuse or hepatitis B and C virus infection); exposure to physical and chemical agents such as radon, asbestos, torotrast, nitrosamines and dioxin.

Which are the symptoms?

Growth of cholangiocarcinoma can lead to obstruction of the biliary tract, so typical signs and symptoms that should alert the patient are jaundice (yellowish discoloration of the skin and sclerae), pain, poorly colored and chalky stools and dark-colored urine. Other common clinical signs of biliary obstruction are itching, increased liver volume, weight loss, and fever.

Diagnosing cholangiocarcinoma is not always easy, especially if there are no typical signs (jaundice, pain, changes in stools and urine) to alert the patient and encourage him to seek medical attention and undergo appropriate tests. If a neoplasm of the biliary tract is suspected, a series of clinical, blood (laboratory), and instrumental examinations are necessary to make a quick and correct diagnosis to confirm or exclude cancer. Laboratory tests include bilirubin, alkaline phosphatase, and glutamyltransferase, as well as the tumor markers CEA and especially CA 19.9, which values are also important for excluding residual disease after surgery, documenting initial disease recurrence, or evaluating the effect of medical therapy.

  • jaundice
  • pain
  • poorly colored stools
  • creamy and dark-colored urine
  • itching
  • enlarged liver
  • weight loss
  • fever

How is it diagnosed?

Instrumental examinations that can be used to make a diagnosis are as follows:

  • abdominal ultrasound (evaluates indirect signs of disease, including the expansion of the biliary tract);
  • CT (computed tomography)
  • magnetic resonance imaging (MRI) and cholangiography-MRI (a special form of MRI that allows visualization of all bile ducts and possible bile outflow obstructions without invasive maneuvers such as retrograde cholangiography and percutaneous cholangiography);
  • ecoendoscopy and retrograde cholangiography or ERCP (Endoscopic Retrograde CholangioPancreatography) – invasive studies performed like a conventional gastroscopy, which allow not only visualization of the main biliary tract but also surgical maneuvers such as prosthesis placement; because it is an invasive maneuver, it can have complications such as pancreatitis;
  • percutaneous transhepatic cholangiography or PTC is performed by inserting a catheter into the biliary tract through the abdominal wall under radiological guidance, allowing visualization of biliary structures and bile drainage. This maneuver can also have complications such as fever, pain, and bleeding;
  • diagnostic laparoscopy: this is a surgical procedure performed under general anesthesia that uses an optical probe to examine the internal organs, helping to exclude the presence of metastases that may be a contraindication to surgical treatment.

Suggested exams

How is it treated?

Diagnosis and treatment of cholangiocarcinoma requires a multidisciplinary approach with synergistic intervention by surgeons, gastroenterologists, radiologists, oncologists and radiotherapists. Currently, surgical resection is the only potentially curable treatment.  In fact, liver resection is necessary to obtain disease-free margins (R0), which are a major determinant of long-term survival.

If surgical treatment is not indicated at the time of diagnosis (about 70% of patients are considered inoperable at diagnosis), the patient is evaluated for initiation of a program of primary chemotherapy and/or radiotherapy (palliative or possibly neoadjuvant) and then surgery is reconsidered based on response to the treatment complex. If the localized neoplasm leads to obstructive jaundice, it is eliminated by placement of a biliary endoprosthesis with ERCP (when technically possible) or percutaneous drainage, and maintenance therapy (e.g., to manage chronic pain) may be prescribed.

In our department, patients with cholangiocarcinoma who are candidates for surgery are managed according to a structured protocol (so-called “preoperative optimization”) aimed at eliminating preoperative symptoms and preventing postoperative complications. This is a pathway, the systematic implementation of which has demonstrated significant benefits for the patient. It consists of:

Diagnostic laparoscopy (eliminates the presence of metastases outside the liver and thus avoids surgery with large incisions in patients who cannot currently benefit from surgical removal of the disease)

Treatment of jaundice: depending on the duration and severity of the jaundice, the need for a percutaneous biliary drainage is evaluated, which keeps the bile ducts of the part of the liver that will not be removed (thus, right drainage in patients who are candidates for left hepatectomy and vice versa) and helps improve the organ function with a prospective follow-up surgery.

MOLECULAR ANALYSES: All patients with cholangiocarcinoma undergo systematic NGS analysis to detect specific mutations/translocations, allowing the use of targeted drugs.

Prognosis and follow-up

A period of chemotherapy or radiotherapy (adjuvant, i.e. performed after surgery) is considered depending on the patient’s characteristics and disease (based on the results of the histological study). At the end of any planned chemotherapy and radiotherapy treatment, the patient will undergo a periodic series of examinations and instrumental and hematologic control to monitor the effect of therapy over a certain period of time and early diagnosis of any recurrence. Planning for follow-up over time is called follow-up and lasts at least 5 years, after which it is assumed that the risk of disease recurrence is comparable to that in the general population.

The term prognosis refers to the long-term results of the treatment offered to the patient; it is statistical data obtained from various studies observing the course of the disease in a large number of patients. It does not mean that the patient will live only 5 or 10 years, but it does indicate the percentage of patients who, according to large studies, were alive 5 or 10 years after treatment. It is important to remember that these statistics are indicative: no doctor can determine exactly what the outcome of treatment will be in a particular patient or quantify survival. In cholangiocarcinoma, prognosis depends on: status of resection margins (better with negative margins); lesions of the lymph nodes (better with no lesions of the lymph nodes); histologic variant (better with papillary); degree of differentiation (better with more differentiated); presence of metastases.

Unfortunately, most patients with cholangiocarcinoma have a poor prognosis, mainly because a significant proportion of them are at an advanced stage at the time of diagnosis; only 20-30% are candidates for surgery, which, as mentioned above, is the only way to cure this tumor. In extrahepatic cholangiocarcinomas, the 5-year survival rate ranges from 15-20% to 42% for localized and resectable tumors and no more than 1% for metastatic tumors.

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Suggested procedures

Where do we treat it?

Within the San Donato Group, you can find Extrahepatic cholangiocarcinoma (Klatskin tumor) specialists at these departments:

Are you interested in receiving the treatment?

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