Bile Duct Cancer
Bile duct cancer is a malignant tumor originating from the bile duct epithelium, accounting for about 3% of gastrointestinal tumors, mostly occurring in 50 ~ 70 years old, with a male to female ratio of 1.4:1. The incidence of bile duct cancer is characterized by geographical distribution, with the highest incidence in northeastern Cambodia, Laos and Thailand, and the incidence in Asians is twice as high as that in whites and blacks. Bile duct cancer is divided into intrahepatic bile duct cancer and extrahepatic bile duct cancer according to the anatomical location, among which, the cholangiocarcinoma of the hilar region (Klatskin tumor) accounts for about 2/3 of extrahepatic bile duct cancer. Surgical resection is still the most effective treatment method, but the current radical resection rate is relatively low, and it is not sensitive to radiotherapy and chemotherapy, so the prognosis is poor. The metastatic pathways of cholangiocarcinoma include local infiltration, vascular invasion, lymphatic metastasis, nerve invasion and abdominal implantation, among which the occurrence of local infiltration is closely related to the differentiation degree of cholangiocarcinoma and is an important factor affecting the surgical resection rate and prognosis. In recent years, with the development of imaging and hepatobiliary surgery, the diagnosis and treatment level of bile duct cancer has been improved to a certain extent, but its overall diagnosis and treatment level and prognosis still need further standardization and improvement.
I. Clinical manifestations
Painless progressive jaundice is the most typical clinical symptom of cholangiocarcinoma, and about 90% of patients have this symptom, so special attention should be paid to ask whether there is abdominal pain to differentiate from bile duct stones. However, it should be noted that progressive cholangiocarcinoma may also have abdominal pain symptoms due to tumor growth or concomitant cholangitis, but the abdominal pain symptoms are not as obvious as those of bile duct stones. Early stage bile duct cancer lacks specific clinical manifestations and is not easily detected. The disease is mostly seen in middle-aged and elderly men, and early symptoms such as epigastric fullness and discomfort, loss of appetite and weight loss are often associated with the disease. Once jaundice appears, the disease no longer belongs to the early stage, and the survival of patients with jaundice and those without jaundice after surgical treatment is very different. Therefore, once patients with early warning symptoms are encountered, they should actively choose relevant auxiliary examinations to achieve early diagnosis and treatment in order to improve the long-term efficacy.
II. Etiology of bile duct cancer
1. Geographical environment The incidence rate of bile duct cancer varies greatly among different countries and regions, which indicates that there are genetic differences among different populations and local specific risk factors in different regions. At present, point mutations, deletions and overexpression of various genes have been found in bile duct cancer. Epidemiological studies have shown that asbestos, PCBs, nitrosamines, isoniazid, thorium dioxide and smoking are weakly associated factors for bile duct pathogenesis, but most patients do not have a history of chemical exposure
2. primary sclerosing cholangitis (PSC): PSC is a chronic cholestatic liver disease with an incidence of bile duct cancer of about 5% to 15%, and the incidence of bile duct cancer with a history of PSC increases by 0.6% to 1.5% per year.
3. intrahepatic bile duct stones: about 4%-11% of Asian intrahepatic bile duct stones can be complicated by intrahepatic bile duct cancer. Repeated episodes of cholangitis and cholestasis can lead to peri-cholangitis, mucosal epithelial hyperplasia, papillary adenomatous hyperplasia, and even bile duct cancer.
4. Congenital malformations of the biliary system: congenital intrahepatic bile duct dilatation (Caroli disease), congenital hepatic fibrosis and common bile duct cysts, etc. The incidence of bile duct cancer in untreated bile duct cysts can be as high as 28%, of which 15% of patients can develop bile duct cancer at an average age of 34 years, with the cumulative risk rate increasing by about 1% per year.
Bile duct parasitosis: In East Asia, parasitic infections (especially Toxoplasma gondii) are caused by the consumption of raw fish.
In East Asia, parasitic infection (especially Toxoplasma gondii) caused by the consumption of raw fish and the deposition of parasite eggs in the bile ducts can lead to the development of bile duct cancer.
6. Others: viral hepatitis, human immunodeficiency virus (HIV), ulcerative colitis, diabetes mellitus, liver cirrhosis, etc. may be related to the development of bile duct cancer.
Diagnostic points
1. Progressive aggravation of obstructive jaundice with epigastric distension, nausea, vomiting, weight loss, etc.
Ultrasound examination is still the first choice for obstructive jaundice caused by bile duct cancer.
CT and MRCP are the ideal non-invasive examination methods, which can clearly and accurately show the site, scope and upper and lower ends of obstruction, visualize the hollow structure of the bile ducts in the hepatoportal area and the location of the lesion, and indicate whether there is portal vein invasion and whether there are metastases in the liver and surrounding lymph nodes, which are useful for guiding treatment. Clinically, it has basically replaced PTC and ERCP and other invasive examinations, and has become the primary examination method after the initial screening of B ultrasound.
4. Elevated CAl9-9 has great significance for the diagnosis of early bile duct cancer. The sensitivity of serum CAl9-9 in the diagnosis of cholangiocarcinoma is 79.34% and the specificity is 89.14%, but CAl9-9 can also be significantly increased in benign diseases such as sclerosing cholangitis and biliary tract infection.
Classification of cholangiocarcinoma
According to the anatomical site, bile duct cancer is divided into intrahepatic bile duct cancer and extrahepatic bile duct cancer with secondary hepatic bile duct as the boundary. Extrahepatic bile duct cancer accounts for 80-90% of all bile duct cancers. According to Longmire’s classification, extrahepatic bile duct cancer can be divided into upper bile duct cancer (above the opening of the cystic duct), middle bile duct cancer (from the opening of the cystic duct to the upper edge of the pancreas) and lower bile duct cancer (from the inner part of the head of the pancreas to before penetrating the duodenal wall). Among them, cholangiocarcinoma of the hilar region accounts for about 70% of extrahepatic cholangiocarcinoma, and cholangiocarcinoma of the middle and lower segments accounts for about 30%. There are four commonly used staging and staging systems for hilar cholangiocarcinoma based on the site and morphology of cholangiocarcinoma, involvement of portal vein and hepatic artery, reserved liver volume, coexisting liver parenchymal lesions, lymph nodes and distant metastases, etc.: (1) Bismuth-Corlette staging; (2) MSKCC T-staging system; (3) TNM staging system of AJCC; (4) International Cholangiocarcinoma Society staging system. At present, the most commonly used clinical staging system for hilar cholangiocarcinoma is Bismuth-Corlette staging system.
V. Treatment Modes
Surgical resection is the only treatment for long-term survival of cholangiocarcinoma patients, and different surgical procedures should be adopted according to the location and staging of the lesion: 1. pancreatic head duodenectomy is suitable for lower or middle-lower cholangiocarcinoma; 2. local resection, lymph node dissection and common hepatic duct jejunostomy Roux-Y anastomosis are suitable for middle cholangiocarcinoma; 3. lobectomy with lymph node dissection is suitable for intrahepatic cholangiocarcinoma; 4. hilar cholangiocarcinoma The surgery of bile duct is more complicated and the treatment modality varies according to the staging.
Currently, the standard surgical procedure for hilar cholangiocarcinoma is lobectomy + extrahepatic bile duct resection + regional lymph node and plexus dissection + hepatic duct-jejunum Roux-en-Y anastomosis. (1) Extrahepatic choledochotomy alone is indicated for Bismuth type I, highly differentiated, hilar cholangiocarcinoma without lymph node metastasis and plexus invasion, and also for palliative resection in high-risk cases with poor physical status or low liver function; (2) Bismuth type II patients require combined hepatic S4b segmental resection or left and right hemicolectomy and caudate lobectomy; (3) Bismuth type IIIa (3) Bismuth type IIIa patients need combined right hemicolectomy or enlarged right hemicolectomy and caudate lobectomy; type IIIb patients need combined left hemicolectomy or enlarged left hemicolectomy and caudate lobectomy; (4) combined central hepatic resection, enlarged hemicolectomy, right triple hepatectomy and left triple hepatectomy are suitable for Bismuth type IV hilar cholangiocarcinoma. (5) Combined pancreaticoduodenectomy is suitable for cholangiocarcinoma of the hilar region invading the lower bile duct and the head of the pancreas. Extended radical surgery can benefit some patients whose R0 resection cannot be achieved by conventional methods.
Palliative treatment of cholangiocarcinoma: Palliative surgery can be performed for patients with hilar cholangiocarcinoma that cannot be surgically resected. At present, most medical centers prefer to perform endoprosthetic stent drainage via the endoscopic route, and for patients who fail in this method, PTCD drainage is an option.
VI. Surgical principles of radical surgery for hilar cholangiocarcinoma
In view of the biological characteristics of multipolar infiltration and metastasis of hilar cholangiocarcinoma, resection of the affected liver parenchyma, caudate lobe and contouring of regional lymph nodes and nerve plexus should be the principle of radical surgery for hilar cholangiocarcinoma. Radical resection is the only effective measure for long-term survival in this group of patients, but if radical resection is not possible, palliative resection is also more effective than biliary drainage alone.
(1) Scope of bile duct removal: the incision line is more than 5 mm from the anterior margin of the tumor on the liver side, and on the pancreas side, it is permanently fixed at the superior margin of the pancreas.
(2) Lymph nodes and plexus contouring: the lymph nodes and plexus tissue in the hilar region, hepatoduodenal ligament, around the common hepatic artery and behind the head of the pancreas should be included. All the tissues in the hepatoduodenal ligament except the hepatic artery and portal vein should be removed to achieve “skeletonization” of the hepatoduodenal ligament.
VII. Follow-up and treatment
Hepatoduodenal cholangiocarcinoma is not sensitive to postoperative radiotherapy and chemotherapy. Radiotherapy can help improve the survival of patients with palliative resection and palliative biliary drainage; the commonly used chemotherapy drugs include 5-fluorouracil, cisplatin, mitomycin C, zilbinol, gemcitabine, oxaliplatin, capecitabine, etc. The treatment efficiency is 0% to 9%, and the average survival time is 2 to 8 months.
The prognosis of hepatoportal cholangiocarcinoma is closely related to the tissue type, differentiation degree, pathological stage, surgical margins and treatment measures of the tumor. At present, the overall 5-year survival rate is about 10%. Radical resection combined with hepatic lobectomy and caudate lobectomy helps to improve the negative surgical margin rate and long-term survival rate of hilar cholangiocarcinoma, and the 5-year survival rate of radical resection can be increased to 30%~60%. However, cholangiocarcinoma of the hilar region has the biological characteristics of multipolar infiltration and metastasis, and the cancer infiltrates along the biliary tree in the proximal and distal bile ducts, while it can break through the biliary tree and invade the adjacent portal vein, hepatic artery and liver parenchyma laterally. Therefore, postoperative patients should be strictly followed up. Usually, patients should be reviewed once a month in outpatient clinic for two years after surgery, and the review should include blood routine, biochemical examination, tumor markers, chest X-ray, ultrasound, and if necessary, enhanced abdominal CT or MRI examination, and lifelong follow-up.