Intrahepatic cholangiocarcinoma

What this tumor is and why it develops

Cholangiocarcinomas are classified by where they arise: intrahepatic, in the ducts inside the liver above the second-order bile ducts; perihilar tumors, where the right and left hepatic ducts join; and distal, in the common bile duct closer to the bowel. This distinction matters because symptoms, examinations and the type of operation depend on it.

Most patients have no obvious cause. Known risk factors include primary sclerosing cholangitis, stones in the intrahepatic ducts, bile duct cysts, liver flukes (opisthorchiasis, clonorchiasis), cirrhosis, chronic hepatitis B and C, and fatty liver disease.

Are there symptoms

Often, no. The tumor grows within the liver without blocking the main ducts, so jaundice is rare and late. Most often the tumor is found by chance on ultrasound or CT, or when dull pain under the right ribs, weakness and weight loss appear.

Because there are no early signs, the tumor is often already large at diagnosis. Large size alone, however, does not make it inoperable: what matters is the number of lesions, their relation to vessels and ducts, and the volume of liver that will remain.

Examinations needed

• Contrast-enhanced CT of the chest, abdomen and pelvis: assessment of the tumor, vessels, lymph nodes and distant metastases.
• Liver MRI with MR cholangiography, which shows the tumor margins, additional lesions and spread along the ducts more precisely.
• Tumor markers CA 19-9 and CEA, which help with diagnosis and follow-up but do not establish the diagnosis; CA 19-9 is also raised in jaundice without cancer.
• Ruling out a metastasis from another organ: under the microscope cholangiocarcinoma resembles metastases of adenocarcinoma of the stomach, bowel, pancreas or breast, so immunohistochemistry of the biopsy is needed, and often upper endoscopy, colonoscopy and other examinations as well.
• Biopsy with molecular analysis: histological confirmation is mandatory before systemic therapy, and in unresectable or advanced disease molecular profiling of the tumor is recommended: some cases show an FGFR2 fusion, an IDH1 mutation or other targets for which targeted drugs exist. If the tumor is clearly resectable, the diagnosis can be confirmed on the resected specimen.
• PET-CT when indicated, if the extent of spread is in doubt.

When surgery is possible

Surgery is considered when the tumor can be removed completely, with clear margins, while preserving enough liver, and there are no distant metastases. Several lesions in the liver, involvement of regional lymph nodes and invasion of major vessels are unfavorable but not always absolute obstacles; such cases are discussed individually.

If the risk of hidden spread is high (a large tumor, several lesions, a high CA 19-9), staging laparoscopy can be performed before a major resection: it detects small peritoneal deposits not visible on CT and avoids a futile major operation.

If surgery is not possible now

The first-line standard for an unresectable tumor in patients in good general condition is chemotherapy combined with immunotherapy. If molecular analysis has found a target, the corresponding targeted drugs are used in later lines. For some patients with disease confined to the liver, local treatments are considered: radioembolization, hepatic arterial infusion chemotherapy, radiotherapy; they are chosen individually.

Sometimes the tumor shrinks after treatment and resection is reconsidered. That is why the follow-up scans during therapy are also reviewed by the surgeon, and the final plan is determined by the MDT.

How the operation is performed

The part of the liver containing the tumor is removed with a margin of healthy tissue. The extent depends on the location: from resection of a few segments to removal of the entire right or left half of the liver. A mandatory step is removal of the regional lymph nodes: of the hepatoduodenal ligament, along the hepatic artery, and for left-sided tumors also of the lesser omentum; they are needed for accurate staging and planning of further treatment.

If the tumor reaches the liver hilum, a segment of the bile duct sometimes has to be removed as well, with bile drainage restored through a loop of small bowel. When the volume of the liver that will remain is insufficient, portal vein embolization is performed before surgery to enlarge the future remnant.

When the tumor’s location and the extent of resection allow, the operation is performed laparoscopically, through several small incisions.

Recovery after surgery

Care follows the enhanced recovery after surgery (ERAS) protocol: early mobilization, early feeding, controlled pain relief. After a major liver resection, liver function and bile drainage are monitored closely in the first days. The remaining liver regains its volume within a few weeks in most cases.

Adjuvant chemotherapy is usually given after surgery. Its regimen and duration are determined by the medical oncologist based on the pathology report and the patient’s condition.

Follow-up

After resection the risk of recurrence remains, most often in the liver. For the first years, CT or MRI and tumor markers are therefore done regularly, every few months, then less often. The schedule is set by the doctor.

A solitary recurrence in the liver found early can, in selected cases, be removed again or destroyed by ablation. If the recurrence is widespread, systemic therapy follows, and the results of the molecular analysis become useful again.

What to bring to the consultation

• contrast-enhanced CT and MRI discs and reports;
• tumor markers CA 19-9 and CEA, blood biochemistry;
• histology, immunohistochemistry and molecular reports, blocks and slides, if a biopsy was done;
• upper endoscopy and colonoscopy reports, if they were done;
• discharge summaries of previous treatment.

If some materials are missing, that is no reason to postpone the consultation: some examinations can be done on site.

The consultation is free of charge. How it goes and how long it takes is described on the page “Oncologist Consultation”.