Cholangiocarcinoma Surgery: Bismuth-Corlette and Resection

Surgery is the only curative treatment for cholangiocarcinoma, the cancer of the bile duct cells. The aim of cholangiocarcinoma surgery is an R0 resection, removing the whole tumour with microscopically clear margins, together with the lymph nodes it drains to. For perihilar tumours, the Bismuth-Corlette classification sets the extent of the operation, from a bile duct resection alone to a right trisectionectomy.

Dr. Ashish George, Principal Consultant & Unit Head Liver Transplant, Fortis Hospital, Shalimar Bagh, New Delhi, India, devoted the second half of his masterclass to intrahepatic and perihilar cholangiocarcinoma: how they behave, how the surgeon decides what to remove, how an extended resection is made safe, and why surgery is worthwhile even when the margin is not perfectly clear. How cholangiocarcinoma differs from hepatocellular carcinoma in risk factors, markers and imaging is set out in the complete guide to the management of primary liver cancers.

Intrahepatic versus perihilar cholangiocarcinoma

The two forms share a cell of origin but behave like different diseases.

Intrahepatic cholangiocarcinoma arises from the bile ducts inside the liver and accounts for about 10 to 15% of primary liver cancers. These are peripherally placed tumours. Because they sit away from the main bile ducts, they do not cause early jaundice; they keep growing, may spread through the lymph nodes, and are usually picked up late. That late detection is the main reason, in Dr. George's assessment, that intrahepatic cholangiocarcinoma can carry a poorer prognosis than other primary liver cancers. On CT these tumours show peripheral enhancement with progressive delayed enhancement, and a peripheral tumour can draw in the liver surface, a sign known as capsular retraction.

Perihilar (hilar) cholangiocarcinoma, historically called a Klatskin tumour, arises around the hilum, where the right and left hepatic ducts join. It blocks the main outflow of bile early, so jaundice appears early and the tumour is found sooner. Its difficulty is anatomical rather than one of late detection: it sits among the liver's major vessels and spreads along the bile duct lining.

Staging versus resectability in cholangiocarcinoma

Cholangiocarcinoma is formally staged with the AJCC (American Joint Committee on Cancer) classification. Dr. George's emphasis is on a more practical question: can the whole tumour be removed? Only patients whose entire tumour is resected have a chance of long-term survival. Stage describes the disease; resectability decides the patient's prospects.

Cholangiocarcinoma surgery: R0 resection and lymphadenectomy

R0 resection. The resection margins must be histologically negative, meaning no tumour cells at the cut edge on microscopy. An R1 resection is one where tumour cells are found at the margin.

Lymphadenectomy. Both intrahepatic and hilar cholangiocarcinomas spread through the lymph nodes, so the perihepatic lymph nodes (those around the liver hilum) must be removed with the tumour.

Appropriate selection of surgical candidates is, in Dr. George's words, extremely important.

The Bismuth-Corlette classification and the operation each type requires

For perihilar cholangiocarcinoma, the Bismuth-Corlette classification describes how far the tumour extends along the bile ducts at the hilum. Each type maps to a different operation.

Type I. The tumour lies below the confluence of the right and left hepatic ducts, so the junction is spared. The surgeon may be able to remove only the bile duct, without resecting liver.

Type II. The tumour reaches the confluence. It may still be resected, with the bile ducts rejoined to the bowel by a hepaticojejunostomy or cholangiojejunostomy. The catch is that these tumours spread along the mucosa (the duct lining), so some resection of the surrounding liver tissue may still be needed for clear margins.

Type IIIa. The tumour extends into the second-order ducts on the right side. Because it now extends into the liver, a major liver resection is required. Dr. George described a tumour involving the common hepatic duct, the hilum, the secondary radicals of the right duct and part of the left duct, treated with a right trisectionectomy (removal of the right liver and segment 4).

Type IIIb. The tumour extends into the second-order ducts on the left side. These tumours require a left or an extended left hepatectomy, removing all the involved liver tissue simply to achieve negative margins.

Type IV. Both sides are involved, and upfront surgery may not be possible.

Why the caudate lobe always comes out

In hilar cholangiocarcinoma, the caudate lobe is always removed. The bile ducts draining the caudate lobe enter the confluence directly, and in the majority of cases they are involved by the tumour. That is why the operation for a type IIIa tumour like the one he described becomes a right trisectionectomy with the caudate, and why the surgical options in perihilar disease are more complicated than in most liver cancers.

Making an extended resection safe: portal vein embolisation

The limiting factor in an extended resection is the future liver remnant, the liver left behind, which must be large enough to sustain the patient.

When a right trisectionectomy is planned, the left lateral section that will remain may be too small. The solution is right portal vein embolisation. The portal vein branch to the right side of the liver is blocked, portal flow diverts preferentially to the left side, the right side shrinks and the left side grows. The tumour can then be resected with an adequate future liver remnant.

Portal vein embolisation is less often needed for a type IIIb tumour, because the right liver, which remains after a left-sided resection, accounts for most of the liver volume and is usually large enough to take care of all liver functions.

Preoperative biliary drainage before cholangiocarcinoma surgery: PTBD or ENBD

Most perihilar patients present with jaundice. Preoperative biliary drainage drains the side of the liver that is going to be preserved, so that the jaundice comes down and the future liver remnant recovers its function before surgery.

Dr. George's indications are specific:

• Cholangitis (infection of the obstructed bile ducts).
• Planned upfront portal vein embolisation before an extended resection, because the future liver remnant needs drainage to have the best chance of growing.

Unless the patient has cholangitis, and particularly where a trisectionectomy is not planned, his unit may resect without any preoperative drainage.

There are two routes. PTBD (percutaneous transhepatic biliary drainage) places a drain through the skin and liver into the bile ducts. ENBD (endoscopic nasobiliary drainage) places a tube endoscopically through the nose into the bile duct. In Dr. George's unit, PTBD is used in the majority of cases. Indicative costs for ERCP-based procedures are listed separately.

Is there a bilirubin level too high for surgery?

Not in Dr. George's practice. His unit has operated on patients with a bilirubin of 30 to 35 mg/dL. This applies to hilar cholangiocarcinoma: intrahepatic tumours usually do not present with jaundice, and by the time an intrahepatic tumour involves the hilum it is usually unresectable.

Vascular involvement and the shift to parenchyma-sparing resections

The major blood vessels run very close to the biliary confluence. The right hepatic artery runs close by, and the portal vein lies immediately behind. Even a very small hilar tumour can involve these vessels and require their resection and reconstruction.

Practice has also moved towards preserving more liver. Five to ten years ago, extended resections in perihilar cholangiocarcinoma typically left only the left lateral section or the right posterior sector. Today, Dr. George's unit can sometimes perform a left or right hepatectomy with the caudate lobe, combined with an extended resection of the bile duct, preserving more liver parenchyma.

Why an R1 resection can still be worthwhile in perihilar cholangiocarcinoma

R0 is the aim in intrahepatic cholangiocarcinoma. For hilar cholangiocarcinoma, Dr. George makes a different argument. Most patients with hilar cholangiocarcinoma do not die of liver failure. They die of cholangitis and the sepsis it causes. A resection, even one with a histologically positive margin, removes the obstructing tumour and restores biliary drainage. Patients who have had an R1 resection therefore do much better than patients who are not offered surgery at all.

Chemotherapy for cholangiocarcinoma: adjuvant, neoadjuvant and advanced disease

Adjuvant. If the patient is stable enough after surgery, capecitabine can be used in the adjuvant setting and is known to improve survival.

Neoadjuvant. Gemcitabine and capecitabine have been used in the neoadjuvant setting to downstage tumours before surgery.

Advanced intrahepatic cholangiocarcinoma. Gemcitabine plus cisplatin forms the first-line treatment. Immunotherapy can be offered, and targeted therapies have been used in studies.

Who receives adjuvant treatment and when. In Dr. George's practice, patients with lymph node invasion, which generally signals advanced disease, or with vascular invasion are referred to the medical oncologist, who decides whether they are fit for adjuvant chemotherapy. Many of these patients are run down after preoperative jaundice and recurrent cholangitis. Once they recover, perhaps after 6 to 12 weeks, adjuvant therapy can be offered; capecitabine is the guideline-recommended adjuvant regimen, as gemcitabine-based adjuvant trials have not shown a benefit. Indicative costs for chemotherapy and hepatectomy are published separately.

Jaundice after liver resection: when to suspect the bile duct

The Pringle manoeuvre, clamping the hepatoduodenal ligament to stop blood inflow to the liver during resection, can raise liver enzymes. In Dr. George's view, it should not cause jaundice from biliary obstruction. A patient who becomes jaundiced after hepatectomy and needs a stent has a bile duct problem.

He outlined the settings in which that happens:

• A narrowed confluence after a right hepatectomy. After a right hepatectomy for an intrahepatic cholangiocarcinoma, with the confluence intact, the stump of the right duct is closed. If the confluence is accidentally narrowed in doing so, the patient may develop jaundice.
• A stricture after a biliary anastomosis. After a hepaticojejunostomy for hilar cholangiocarcinoma, a bile leak can later lead to a biliary stricture and postoperative jaundice that needs stenting.
• Preoperative radiotherapy. Radiation can compromise the blood supply of the bile duct, and an anastomosis made on that duct may stricture.

Follow-up imaging and tumour markers after treatment, including why CT or MRI is preferred to ultrasound after cholangiocarcinoma surgery, are covered in the complete guide. The other primary liver cancer, hepatocellular carcinoma, is treated on a different logic set out in HCC treatment: resection, ablation or liver transplant. For the interventional procedures that support this surgery, including PTBD and portal vein embolisation, see Dr. Shobhit Singh's guide to hepatobiliary interventional radiology. Doctors' questions on bilirubin thresholds, adjuvant drugs and jaundice after the Pringle manoeuvre are answered in the Live Discussion.