Cholangiocarcinoma refers to malignant tumors originating from the extrahepatic bile ducts, ranging from the confluence of the left and right hepatic ducts to the lower end of the common bile duct. Primary cholangiocarcinoma is relatively rare, accounting for 0.01% to 0.46% of routine autopsies, 2% of tumor-related autopsies, and 0.3% to 1.8% of biliary tract surgeries. In Europe and America, gallbladder cancer is 1.5 to 5 times more common than cholangiocarcinoma, while data from Japan show that cholangiocarcinoma is more frequent than gallbladder cancer. The male-to-female ratio is approximately 1.5 to 3.0. The disease predominantly affects individuals aged 50 to 70, but it can also occur in younger people.

bubble_chart Pathological Changes

1. The sites of occurrence of extrahepatic bile duct cancer. Anatomically, based on the site of cancer occurrence, extrahepatic bile duct cancer can be classified into: ① Left and right hepatic duct cancer; ② Common hepatic duct cancer; ③ Cystic duct cancer; ④ Cancer at the confluence of the common hepatic duct, cystic duct, and common bile duct; ⑤ Common bile duct cancer.
2. Gross morphology of extrahepatic bile duct cancer: Extrahepatic bile duct cancer can be divided into three types based on gross morphology: ① Wall-infiltrating type: Can occur in any part of the bile duct and is the most common. Due to thickening of the affected duct wall, the lumen may narrow or become stenotic, leading to obstruction. ② Nodular type: Less common than the wall-infiltrating type, typically seen in more advanced stages of bile duct cancer. The diameter of the cancerous nodules can range from 1.5 to 5.0 cm. ③ Intraluminal papillary type: The rarest, can occur in any part of the bile duct but is even less common at the confluence. This type can completely obstruct the bile duct lumen. In addition to growing primarily into the lumen, the cancerous tissue can also infiltrate further into the duct wall.
3. Histological types of extrahepatic bile duct cancer: Based on the type of cancer cells, degree of differentiation, and growth pattern of the cancerous tissue, extrahepatic bile duct cancer can be classified into the following six types: ① Papillary adenocarcinoma: Almost exclusively intraluminal papillary type, with rare cases of wall-infiltrating type. ② Well-differentiated adenocarcinoma: The most common in bile duct cancer, accounting for over two-thirds, and can occur in any location. The cancerous tissue infiltrates and grows within the duct wall, encircling the entire wall. The infiltrating cancer tissue forms glandular structures of varying sizes and irregular shapes, some of which may expand into cystic cavities. ③ Poorly differentiated adenocarcinoma: Adenocarcinoma with poor differentiation, where part of the cancerous tissue forms glandular structures and part forms irregular solid masses, also diffusely infiltrating the duct wall. ④ Undifferentiated carcinoma: Relatively rare. Some small cell undifferentiated carcinomas are similar to undifferentiated carcinomas of the gallbladder, with cancer cells diffusely infiltrating the bile duct wall and minimal stroma. The cancerous tissue is highly invasive, often spreading to surrounding adipose tissue or adjacent organs. ⑤ Signet-ring cell carcinoma: Rare. Like signet-ring cell carcinomas of the gallbladder or gastrointestinal tract, it consists of mucus-containing cancer cells with varying degrees of differentiation. The cancer cells lack a defined structure and infiltrate diffusely. ⑥ Squamous cell carcinoma: Extremely rare. Its histological morphology is identical to that seen in other organs.
4. Spread and metastasis of extrahepatic bile duct cancer: In the early stages, metastasis is rare, with direct spread primarily along the bile duct wall upward or downward. For example, cancer in the upper hepatic duct can directly invade the liver, which is more common than in the middle or lower segments. The most common metastasis is to the lymph nodes at the hepatic hilum, but it can also spread to lymph nodes in other abdominal regions. Hematogenous metastasis is generally rare unless the cancer is at an advanced stage. Among all sites of bile duct cancer, liver metastasis is the most common, especially in high-position bile duct cancer, where the cancerous tissue easily invades the portal vein, forming cancerous thrombi that can lead to liver metastasis. It can also metastasize to adjacent organs such as the pancreas and gallbladder.

bubble_chart Clinical Manifestations

Progressive obstructive jaundice is the main symptom of bile duct cancer, often accompanied by cutaneous pruritus. About half of the patients experience mild to moderate epigastric distension, fullness, pain, and fever. A minority of patients may exhibit manifestations of cholangitis, while approximately half experience loss of appetite and weight loss. The presence of gallbladder enlargement varies depending on the location of the bile duct cancer. The liver is often enlarged and can be palpated below the costal margin or xiphoid process, with a firm texture and minimal tenderness. In the late stage (third stage), symptoms of portal hypertension such as splenomegaly and ascites may appear.

bubble_chart Auxiliary Examination

In addition to paying attention to the above clinical manifestations, the following auxiliary examinations should be performed.

**Laboratory tests:** Mainly show abnormal liver function indicative of obstructive jaundice, such as elevated bilirubin and alkaline phosphatase.
1. **Ultrasound examination:** Repeated and careful B-ultrasound examinations can reveal dilated bile ducts, the site of obstruction, and even tumors. The ultrasound images of bile duct cancer may appear as mass-like, cord-like, protruding, or thrombus-like. Intrahepatic bile duct cancer often presents as a mass or cord-like structure, hilar cancer as cord-like, and distal bile duct cancer as protruding. A thrombus-like ultrasound image in the hilar region may indicate hilar cancer, gallbladder cancer, or metastatic cancer. Since bile duct dilation occurs before jaundice, B-ultrasound has diagnostic value for early-stage bile duct cancer.
2. **PTC (Percutaneous Transhepatic Cholangiography):** This is the primary method for diagnosing bile duct cancer. It can reveal the location and extent of the cancer, with a diagnostic accuracy rate of 94–100%.
3. **CT (Computed Tomography):** The basic CT findings of bile duct cancer include: 1. Marked dilation of the bile ducts proximal to the tumor. 2. Thickening of the bile duct wall near the tumor, which becomes more clearly enhanced during contrast scanning, with irregular narrowing and deformation of the lumen. 3. A soft tissue-density tumor shadow is usually detectable, with a CT value of 50 Hu, which enhances to 60–80 Hu during contrast scanning. 4. Most tumors grow infiltratively along the bile duct wall, with thickened walls and poorly defined edges that become more visible upon enhancement. 5. A few tumors grow polypoid or nodular into the lumen, with nodules appearing as soft tissue density. 6. Tumors may infiltrate outward, blurring the duct wall edges, often invading the gallbladder, liver, adjacent blood vessels, and lymphatic tissue, appearing as irregular, heterogeneous soft tissue shadows with indistinct boundaries.
4. **ERCP (Endoscopic Retrograde Cholangiopancreatography):** Allows direct observation of the duodenal papilla, and contrast imaging can display the bile duct distal to the obstruction.
   **Angiography:** Angiography can better determine whether bile duct cancer is resectable.
5. **Cytological examination:** Based on PTCD (Percutaneous Transhepatic Cholangiography and Drainage), the sinus can be expanded to insert a fiber-optic cholangioscope for direct observation and biopsy of the mass. During PTC or PTCD, bile can be aspirated for cytological examination.

6. bubble_chart Treatment Measures

   1. Surgical Treatment of Bile Duct Cancer

      (1) Selection of surgical methods for resectable hilar cholangiocarcinoma:

      ① Resection of hilar bile duct, common bile duct, and gallbladder, with biliary-enteric anastomosis. Suitable for common hepatic duct cancer without invasion of liver parenchyma.

      ② Resection of the quadratic lobe or partial right anterior lobe, along with hilar bile duct and extrahepatic bile duct resection, and biliary-enteric anastomosis. Suitable for common hepatic duct cancer or confluence bile duct cancer.

      ③ Resection of the quadratic lobe or left hemihepatectomy, along with hilar bile duct and extrahepatic bile duct resection, and biliary-enteric anastomosis. Suitable for left hepatic duct and common hepatic duct cancer.

      ④ Resection of the quadratic lobe or right hemihepatectomy, along with hilar bile duct and extrahepatic bile duct resection, and biliary-enteric anastomosis. Suitable for right hepatic duct and common hepatic duct cancer.

      ⑤ Extended hemihepatectomy or trisegmentectomy, along with hilar bile duct, extrahepatic bile duct, and partial caudate lobe resection, and biliary-enteric anastomosis. Suitable for left or right hepatic duct cancer invading secondary bile ducts and caudate lobe bile ducts.

      ⑥ Palliative resection. Resection of the quadratic lobe, hilar bile duct, and extrahepatic bile duct, with biliary-enteric anastomosis, leaving residual cancerous tissue such as caudate lobe bile ducts or the anterior wall of the portal vein.

      ⑦ For cases where the main trunk, confluence, or anterior walls of the left and right branches of the portal vein are invaded, the affected venous wall is resected and vascular repair and reconstruction are performed, followed by postoperative intracavitary radiotherapy.

      (2) Palliative surgery for hilar cholangiocarcinoma: Biliary-enteric internal drainage is the preferred palliative surgical method. The principle is to place the biliary-enteric anastomosis as far away from the lesion as possible. The site of biliary-enteric anastomosis is selected based on PTC findings of dilated bile ducts. In some cases, due to tumor invasion of the hilum or the presence of liver atrophy-hypertrophy complex, anastomosis and drainage of the atrophic lobe bile ducts are of little value. Exposure of the hypertrophic lobe bile ducts is difficult, leaving many unresectable cases with only tube drainage. Common methods include dilation of cancerous strictures followed by placement of the largest and stiffest possible T-tube, U-tube, or internal stent. The T-tube can be placed through the common bile duct or the liver. To prevent slippage, the drainage tube should be sutured and fixed to the bile duct wall and surrounding tissues, and a proximal jejunostomy should be created for postoperative bile reinfusion and, if necessary, tube feeding. Non-surgical tube drainage commonly uses PTCD, and internal stents can also be placed after expanding the PTCD sinus, traversing the stricture.

      (3) Resection of middle and lower bile duct cancer: Middle and lower bile duct cancers are less common than hilar and papillary cancers. Currently, most scholars advocate pancreaticoduodenectomy as the surgical approach. For unresectable middle and lower bile duct cancers, the aforementioned palliative methods can be used.

   2. Chemotherapy: Postoperative apoplexy involving meridians, gastric web membrane with stirred pulse, catheter insertion to the liver stirred pulse, placement of a drug pump catheter, and subcutaneous pump implantation for postoperative drug administration via the pump. Commonly used chemotherapeutic drugs are 5-Fu and MMC.
   3. Radiotherapy: Intraoperative radiotherapy, postoperative targeted radiotherapy, and staged internal irradiation. Radical dose radiotherapy has some effect on advanced-stage bile duct cancer, as it can cause cancer cell degeneration, necrosis, and growth inhibition, thereby prolonging the survival of patients with advanced-stage bile duct cancer.

   bubble_chart Prognosis

   The prognosis for cholangiocarcinoma is extremely poor. The average survival time for the surgical resection group is generally 13 months, with very few surviving for 5 years. If only internal or external biliary drainage is performed, the average survival is merely 6 to 7 months, rarely exceeding 1 year.