Diagnosis
The classic diagnostic pattern of hilar cholangiocarcinoma is: jaundice + dilated intrahepatic bile ducts + normal caliber of extrahepatic bile ducts + empty gallbladder + occupying lesions in the hilar region, which is not difficult to diagnose, but it is mostly in the middle and late stages.
I. Imaging examinations.
1, B-mode ultrasound scan is non-invasive, repeatable, simple, and economical and has become the preferred screening method for the cause of obstructive jaundice. Its advantages are.
(i) It can show dilated intrahepatic bile ducts and empty extrahepatic bile ducts and gallbladder.
(ii) The lumen distal to the dilated bile duct is abruptly truncated and occluded, and a moderate or hypoechoic mass shadow can be detected.
③The location and infiltration range of the tumor can be clarified; the relationship between the tumor and the hepatic artery and portal vein, and the presence of cancerous thrombus in portal vein.
④It can also understand whether there is metastasis in the liver and the metastasis of extrahepatic lymph nodes.
The shortcoming of ultrasound is that the clarity is not high, which can be affected by obesity, rib arch obscuration, intestinal gas and the operator itself.
Figure 1 Ultrasound images of hilar cholangiocarcinoma: a. Infiltrative type, b. Mass type.
According to the ultrasound image, bile duct cancer in the hilar region can be divided into 4 types: 1. Mass type: the mass has no obvious boundary, irregular shape, slightly high and uneven echogenicity. The affected bile ducts are penetrated in the uneven echogenic area, and the dilated bile ducts around the tumor are truncated, and the mass can be seen protruding into the lumen at the truncated bile ducts; 2. 4. Thick-walled small papillary type: The intrahepatic bile ducts are dilated and cystic in shape, with the wall thickened up to 5 mm, papillary protrusions are seen on the mucosa, and mucus-like material is echoed in the lumen. Due to the diverse pathological types of cholangiocarcinoma in the hilar region, the sonographic manifestations are also diverse, including hypoechoic, moderately hypo- or moderately hyper-echoic, and hyper-echoic. Tumors of small bile ducts are more difficult to diagnose by ultrasound. Tumors of larger bile ducts may cause dilatation of the distal bile ducts. In addition to infiltrating and spreading along the bile duct wall, cholangiocarcinoma of the hilar region often infiltrates into the surrounding liver tissues with the bile duct as the center, resulting in indistinct boundaries. The early tumor of bile duct is difficult to recognize, and the lesion is mainly fibrotic. Ultrasound only shows stiffness and thickening of bile duct wall, or similar to stone image, which is easy to miss or misdiagnose.
2. CT The image of CT scan is clearer and not affected by obesity, intestinal gas and subjective factors of the operator, so it is the preferred method to diagnose cholangiocarcinoma of the hilar region.
CT can objectively show the location and size of tumor, the relationship between tumor and surrounding tissues; show the morphological changes of liver lobe (hypertrophy or atrophy), the relationship between tumor and caudal lobe; interruption of continuity between dilated left and right hepatic ducts, which can provide accurate obstruction level and signs of dilated intrahepatic bile duct. Enhanced scan can make the tissue structure more clear. Spiral CT can obtain uninterrupted image information of human anatomical structures. Combining this special image acquisition method with intravenous contrast injection (i.e., enhancement scan), multiple image processing methods are used to display vascular images. Therefore, spiral CT can replace angiography to show the structure of hepatic artery and portal vein system and understand the involvement of hepatic artery and portal vein system.
Figure 2 CT portal vein phase scan of cholangiocarcinoma in the hepatic portal region: a nodular soft tissue shadow is seen above the right branch of portal vein, with lower density than the liver parenchyma but higher density than the dilated bile duct.
For localized cholangiocarcinoma lesions, CT can reveal a mass shadow in the hilar region or localized irregular thickening of the bile duct wall. The mass of cholangiocarcinoma is hypointense at the early stage of enhancement (arterial phase), and the mass gradually increases in density at the portal phase, which means delayed enhancement.
Cholangiocarcinoma of the hilar region is mostly devoid of blood vessels, and the dense fibrous matrix surrounding the glandular lumen retains the contrast agent for a longer period of time, therefore, it often appears hypodense or isodense in the arterial phase and relatively dense in the portal vein phase or equilibrium phase during CT enhancement.
Indirect images of cholangiocarcinoma show signs of bile duct obstruction and liver atrophy in the area of the corresponding bile duct drainage. If multiple small nodular hypointense images are seen in the liver at the same time, it indicates intrahepatic metastasis of cholangiocarcinoma. If the bile duct cancer is small or the tumor grows along the duct wall and the direct signs are not obvious, the diagnosis of bile duct cancer mainly relies on the indirect signs of CT, i.e. the dilatation of bile ducts inside and outside the liver, scope, size of gallbladder and hilar lymph nodes to determine the location and nature of bile duct lesions.
3. Magnetic resonance cholangiography (MRCP) has obvious advantages compared with ultrasound and CT.
(1) Non-invasive, non-invasive, non-radioactive, no need for contrast, and easily accepted by patients.
(ii) It can clearly show the whole bile duct, which is more accurate for clinical staging and preoperative assessment.
(iii) safe and without complications.
(4) MRCP is feasible for those who cannot perform transendoscopic retrograde cholangiopancreatography (ERCP) or failed ERCP examination.
⑤ It can guide the location of percutaneous transhepatic percutaneous choledochal drainage (PTCD) and endobiliary stent placement.
In case of hilar lymph node metastasis, CT and MRI show a hilar mass, while MRCP shows the right and left hepatic ducts are narrowed by compression or destroyed. If there is intrahepatic metastasis, scattered low signal shadow can be seen.
Figure 3 MRI of cholangiocarcinoma of the hilar region: visible entanglement of the hilar non-bile ducts, dilated intrahepatic bile ducts, and atrophy of gallbladder, type IV
4. Percutaneous transhepatic percutaneous cholangiography (PTC)
It can display the intrahepatic bile duct morphology in detail, directly show and clarify the site of tumor, the extent of tumor involvement in hepatic duct, the relationship between tumor and hepatic duct confluence. However, it is an invasive test, which may cause bleeding, bile leak, biliary tract infection and pneumothorax. Very few patients may have metastasis from the punctured tract, and its overall complication rate is 1%-7%. Meanwhile, PTC can only show the dilated bile duct above the obstruction, and for type IV hilar cholangiocarcinoma, left and right lobe perforation angiography must be performed separately to fully show the dilated bile duct and the site of obstruction, and this increases the risk of complications, and the placement of PTCD to reduce jaundice is controversial.
5. Transendoscopic retrograde cholangiopancreatography (ERCP)
It can show the lower boundary of the tumor and the biliary tract below the obstruction. If PTC and ERCP are performed simultaneously, they can complement each other and show the upper and lower margins of the tumor completely, which is important for judging the size and scope of the tumor and deciding the surgical plan. The most fatal complication of ERCP is that the contrast can cause upstream infection inducing acute cholangitis, infectious toxic shock or multiple liver abscesses, which can bring difficulties to treatment and even lose the time of surgery. With the development and popularity of CT, MRI, MRCP and ultrasound technology, PTC or PTCD is now largely not used, and ERCP is rarely used due to its fatal complications.
Figure 4 ERCP images of cholangiocarcinoma of the hilar region: a. Stenosis of the upper segment of the common hepatic duct with no involvement of the right and left hepatic ducts (type I); b. Stenosis of the upper segment of the common hepatic duct and the beginning segment of the right hepatic duct with failure to show the right intrahepatic bile duct (type IIIa)
6.Digital subtraction angiography (DSA)
DSA diagnosis of cholangiocarcinoma in the arterial phase mainly shows the invasion of peripheral arteries, usually the left and right hepatic arteries or the intrinsic hepatic artery wall irregularity, stenosis or obstruction. At present, due to the development of CT and MRI technology, DSA is no longer used as a routine means to diagnose hepatoportal cholangiocarcinoma.
7.Positron emission tomography (PET) FDG-PET examination of bile duct cancer has high sensitivity and specificity, but it cannot make effective differentiation between bile duct inflammatory disease and bile duct cancer, however, 20% of patients are diagnosed as tumor metastatic disease by FDG-PET scan. A large number of studies are still needed to determine the accuracy of FDG-PET in detecting metastases. If the detection rate is confirmed to be 20%, then the number of surgeries avoided by this test is still very significant and it is valuable to perform this test.
EUS biopsies are more sensitive than intraluminal biopsy techniques, with 91% accuracy, 89% sensitivity and 100% specificity, respectively.
9. Laparoscopy The use of laparoscopic findings as a basis for tumor staging should be considered after the completion of conventional imaging, with the aim of detecting metastases that may be missed by conventional imaging techniques and thus avoiding unnecessary cesarean surgery. Metastases as small as 1 mm are well below the detection limit of radiological imaging but may be detected by examination of the peritoneum or liver surface. Laparoscopy can be performed either as a stand-alone procedure or in conjunction with surgical resection under the same general anesthesia. Laparoscopy has a low sensitivity for T1 stage lesions but a sensitivity of more than 30% for T2/T3 lesions. Laparoscopy is currently limited to use in cases of high suspicion of unresectability.
Second, tumor markers.
1.CA19-9
The specificity of elevated CA19-9 for the diagnosis of hepatoportal cholangiocarcinoma is very low. In the absence of jaundice and cholangitis, serum CA19-9 values >37 kU/L in 86% (47/55) and >222 kU/L (6 times the normal value) in 71% (39/55) of patients with hepatoportal cholangiocarcinoma. The specificity of CA19-9 >300 U/ml was 87%. CA19-9 is not a specific marker for cholangiocarcinoma, but can also be elevated in pancreatic cancer, intestinal malignancies and gynecologic malignancies. In patients with PSC, CA19-9 is less specific if the cut-off value is taken at 37 U/ml. If the cut-off value is taken at 100 U/ml, it seems to provide the best balance between sensitivity and specificity for PSC patients. a significant increase in CA19-9 value can help in the diagnosis of cholangiocarcinoma of the hilar region.
2.Cholangiocarcinoma-associated antigen test
Cholangiocarcinoma-related antigen (CCRA) is a new antigenic substance discovered from human cholangiocarcinoma tissue in recent years. In normal human serum, CCRA is <28.95 g/L. In cholangiocarcinoma, serum CCRA concentration increases significantly.
The positive rate of CCRA and carbohydrate antigens (especially CA19-9) is similar in cholangiocarcinoma, but the positive rate of CCRA in other GI tumors is very low. This is of great value for the diagnosis and differential diagnosis of cholangiocarcinoma.
III. Cytological examination.
Obtaining bile for exfoliative cytology by PTC or ERCP technique has high diagnostic specificity but rather low sensitivity, probably because the cells are denatured and lysed in bile or the tumor is encapsulated by proliferating connective tissue. In order to improve the diagnostic sensitivity, Mo-handas (1994) used a dilator to dilate the bile duct stenosis and then extracted bile, and the positive rate increased from 27% to 63%, which may be due to the fact that after the stenosis was dilated, the free cancer cells were more likely to enter the bile. When PTC or ERCP examination reveals bile duct strictures suspected of having cancerous lesions, a cytobrush can be placed to repeatedly brush the bile duct strictures and obtain specimens for cytological examination, or biopsy the lesions through pancreaticoduodenoscopy. These two methods have high diagnostic specificity, almost 100%.