Hepatoportal cholangiocarcinoma is a mucosal epithelial carcinoma occurring in the left hepatic duct, right hepatic duct, left and right hepatic duct bifurcations and the upper part of the common hepatic duct, also known as klatskin tumor. According to Launois et al, klatskin tumors account for about 58%-75% of extrahepatic bile duct cancers. Because of the lack of understanding of this disease in the past, coupled with the special anatomical location of the tumor and its early invasion of vascular nerves, lymphatic tissues and adjacent liver tissues, its early diagnosis and treatment are difficult and its prognosis is poor. In recent years, with the development of medical imaging, biochemistry, pathology, surgery and other related disciplines, great progress has been made in the diagnosis and treatment of this disease in clinical practice. The author reviews the relevant literature at home and abroad in recent years and reviews the following. Department of Hepatobiliary Surgery, The First Hospital of Harbin Medical University, Ma Yong 1 Diagnosis 1.1 Clinical manifestations Patients with hepatoportal cholangiocarcinoma have no specific clinical manifestations before the bile duct is obstructed by tumor, and only have early non-specific symptoms such as epigastric discomfort, loss of appetite and weakness, which are not easily diagnosed. Most patients present with obstructive jaundice, accompanied by generalized itching, left upper abdominal pain and white clay-colored stool, which are already in advanced stage, so the clinical manifestations have little significance for the early diagnosis of this disease. yj et al. reported that the incidence of jaundice, itching and abdominal pain in patients with hepatoportal cholangiocarcinoma were 94.5%, 56.6% and 33.8%, respectively. 1.2 Imaging examination 1.2.1 Ultrasound scan Ultrasound shows: (1) large liver and dilated intrahepatic bile ducts; (2) non-dilated common bile duct; (3) empty gallbladder; (4) strong echogenic masses in the common bile duct or left or right hepatic duct, but no acoustic shadow. The sensitivity, specificity and accuracy of ultrasound in diagnosing cholangiocarcinoma of the hilar region are 85.9%, 76.9% and 84.4%, respectively. ultrasound can also indicate the infiltration of the tumor along the hepatic duct or its spread outside the duct, the presence of metastatic lesions in the liver, and the presence of intra-abdominal lymph node enlargement, portal vein obstruction and ascites, etc. Color Doppler ultrasound (CDU) can understand the relationship between tumor and hepatic artery and portal vein, and can clearly see the invasion of portal vein by tumor, with an accuracy rate of 86%, and the diagnostic rate of relationship between tumor and hepatic artery is 77.3%. ultrasound and CDU together can make the diagnosis of tumor staging and provide more valuable information for the judgment of the possibility of surgical resection. In addition, the use of endoscopic ultrasound (EUS) during surgery to explore the extent of biliary tumor infiltration can avoid the influence of gastrointestinal gas with an accuracy of 86%. It is also believed that asymmetric thickening of the bile duct wall, bumpy outer edge of the lumen, stiffness of the duct wall or papillary shape of the duct are tumor-specific. Although intravascular ultrasonography such as portal vein is helpful to determine the possibility of surgical resection and its accuracy rate is higher than 95%, it has many complications and has been applied less.1. 2. 2 CT scan Although B ultrasound examination has its unique advantages, it is easily affected by the operator’s experience and intestinal lumen gas and other factors. And CT can make up for the deficiency of B ultrasound, objectively showing the location and size of tumor, the relationship between tumor and surrounding tissues, morphological changes of liver lobes, the location and morphology of dilated bile ducts and the relationship between tumor and caudate lobe. Therefore, ultrasound should be chosen to be used in combination with CT examination. In addition to diagnosing smaller lesions, spiral CT can also replace angiography to show vascular involvement in the hilar region. The spiral CT multi-phase scan can directly show the mass in the hilar bile duct, slight enhancement in the arterial and portal vein phases, and delayed scan with continuous obvious enhancement and different degrees of dilatation of the intrahepatic bile ducts, and also can observe the metastasis of intrahepatic, peri-pancreatic head and retroperitoneal lymph nodes, the relationship between the lesion and bilateral secondary bile duct branches, and the involvement of portal vein, which are of great value for the selection of surgery and operation.
1.2.3 Percutaneous transhepatic cholangiography (PTC) PTC can obtain clear X-ray pictures of the bile duct tree, showing the morphology of the obstructed upper bile duct and the site of tumor obstruction, and is the traditional X-ray examination method for hilar cholangiocarcinoma. However, when the bile duct is obstructed at the bifurcation, bilateral punctures are required to show the bile duct system separately. As an invasive test, it can cause complications such as bile leak, bleeding and biliary tract infection due to high intra-biliary pressure, poor coagulation mechanism and low immunity of the obstructed patient, with an incidence of 1% to 7%. ERCP can directly observe the carcinoma foci in the papillae of the lower bile duct, which is mainly suitable for obstructive jaundice where the dilatation of intrahepatic bile ducts is not obvious, and can clearly show the biliary system distal to the obstruction, which is more suitable for the diagnosis of low-level biliary obstruction. However, because cholangiocarcinoma is often infiltrated in the submucosa, the positive rate of ERCP biopsy is not high, and it often causes complications such as biliary tract infection and pancreatitis.1.2.5 Magnetic resonance imaging Magnetic resonance imaging can do bile duct imaging in three planes, and magnetic resonance pancreaticobiliary imaging (MRCP) is currently a non-invasive, non-contrast, safe and simple diagnostic imaging technique, which can obtain intuitive three-dimensional images of the pancreaticobiliary system Yeh et al. concluded that MRCP is superior to ERCP after comparing 40 clinical cases of hilar bile duct obstruction, and Zidi et al. concluded that MRCP is superior to ERCP in terms of elective surgery. Zhou et al. compared the accuracy of US, CT, PFC, ERCP and MRCP and concluded that MRCP was superior to the others in terms of both the location and the nature of the tumor. 1.2.6 Digital subtraction angiography (DSA) shows The arterial phase of DSA diagnosis of cholangiocarcinoma mainly shows the invasion of peripheral arteries, usually the left and right hepatic arteries or the intrinsic hepatic artery wall irregularity, stenosis or obstruction, and in some cases, microscopic tumor vessels can be seen around the invaded arteries; in the capillary phase, tumor staining can be seen, and the venous phase is poorly visualized when the portal vein and its branches are invaded. 1.2.6 Digital subtraction angiography (DSA) shows the relationship between human hepatic vessels and tumor and the invasion by tumor. 1.3.1 Cholangiocarcinoma-related antigen (CCRA) CCRA is a new antigen discovered in recent years from human cholangiocarcinoma tissues with a molecular weight of 1.14×lO5 U. CCRA is <28.95 g/L in normal human serum, but its concentration increases significantly in cholangiocarcinoma. The positive rate of CCRA and carbohydrate antigen (especially CA19-9) in cholangiocarcinoma is similar, 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.1.3.2 CA19-9 In the absence of cholangitis, serum CA19-9 values in patients with cholangiocarcinoma of the hilar region were greater than 37 ku/L in 86% and greater than 222 ku/L (6 times the normal value) in 71%. -IL-6 is a pleiotropic cytokine consisting of 184 amino acids that promotes acute inflammatory response and is not measurable under normal conditions, but is significantly elevated in hepatocellular carcinoma and cholangiocarcinoma. The positive value of IL-6 as a serum marker was 83.3% for cholangiocarcinoma and 81.3% for hepatocellular carcinoma. The sensitivity of increased IL-6 in cholangiocarcinoma is 100%, and the specificity is 91.4%, and the serum IL-6 value of cholangiocarcinoma patients is positively correlated with the tumor load, and its activity mean and median values are significantly higher than those of other tumors. CEA is a glycoprotein with a molecular weight of 1.8×10e5 U. It is present in the serum, bile and bile duct epithelium of patients with bile duct cancer. Bile cEA [50.2±5.8) ng/ml] was significantly higher in patients with cholangiocarcinoma than in patients with benign biliary strictures [(1±3.9) ng/ml], suggesting that measurement of CEA in serum and bile is useful for early diagnosis of cholangiocarcinoma, evaluation of residual tumor, and prognosis.1.3.5 Cytological examination was performed by obtaining bile for exfoliative cytology by PTC or ERCP techniques or by repeatedly brushing the bile duct strictures with a cytobrush. The bile duct stenosis is repeatedly brushed and the specimen is obtained for cytological examination. The high specificity but low sensitivity of bile examination may be due to the degeneration and lysis of cells in bile or the encapsulation of the tumor by proliferating connective tissue. In order to improve the diagnostic sensitivity, Mo-handas et al. used a dilator to dilate the bile duct stenosis and then extracted bile in 1994, and the positive rate increased from 27% to 63%, probably because the free cancer cells shed after the stenosis was dilated could enter the bile more easily. 1.4 Genetic diagnosis of cholangiocarcinoma with codon 12 mutation in the K-raS gene is currently a hot research topic in China and abroad. Hidaka et al. examined 37 patients with bile duct cancer and found that the mutation rate of K-raS gene was 30%, and pointed out that the mutation rate increased gradually with the location of bile duct cancer from top to bottom. Thus, whether K-raS gene is mutated or not could be a factor affecting prognosis. Based on the above findings, the prediction of K-raS gene testing will provide a favorable basis for early diagnosis of cholangiocarcinoma and may also be a factor affecting prognosis.
2 Treatment There are many methods for treating cholangiocarcinoma of the porta hepatis, and each has its own advantages and disadvantages, but clinically, surgical resection should still be the main treatment, supplemented by various comprehensive treatment methods, in order to achieve the purpose of improving the quality of life and increasing the survival rate.2. 1 Genlo}shengectomy With the development of diagnostic techniques and advances in surgical techniques as well as changes in treatment attitudes, the surgical resection rate of this disease has been significantly improved. At present, Zhou Ningxin et al. in China reported that the radical resection rate of hilar cholangiocarcinoma is 37.6%-43%, and the average radical resection rate in foreign countries is 34.8%. Surgical resection is the only possible way to obtain cure for hilar cholangiocarcinoma, so a positive attitude should be adopted to strive for better results. Radical resection includes extrahepatic biliary resection, “skeletonization” of blood vessels on the hepatoduodenal ligament, extensive resection of fibrofatty tissue, nerves and lymph on the duodenal ligament, resection of one liver lobe if necessary, and reconstruction of bile duct jejunostomy. Since the cholangiocarcinoma of the hilar region mainly infiltrates up and down along the bile duct wall and spreads to the perineural and lymphatic spaces, thus making the important structures around the bile duct such as hepatic artery, portal vein and liver parenchyma vulnerable to invasion, among which the residual cancer cells in the connective tissue of hepatoduodenal ligament is an important factor for the recurrence of cholangiocarcinoma of the hilar region after resection. Therefore, some scholars propose combined partial hepatectomy and, if necessary, combined pancreaticoduodenectomy, which is the so-called extended radical surgery. Most cholangiocarcinomas in the hilar region have caudate lobe infiltration, and caudate lobe resection is required for those invading the confluence or left and right hepatic ducts, and it is considered that whether to combine caudate lobe resection is one of the main relevant factors affecting the long-term survival of patients with hilar cholangiocarcinoma. Partial hepatectomy combined with reconstruction after portal vein and/or hepatic artery resection has also been proposed for the treatment of advanced hilar cholangiocarcinoma. This procedure can not only improve the resection rate of hilar cholangiocarcinoma, but also reduce the chance of tumor recurrence and prolong survival, but the surgical risk is relatively increased. Most of the patients with hilar cholangiocarcinoma have obstructive jaundice and impaired liver function, and an overly extensive hepatic resection is bound to increase the incidence of postoperative complications and mortality. Therefore, some scholars have used preoperative embolization of the affected hepatic artery and portal vein to shrink the volume of the liver within the resected area and increase the volume and function of the rest of the liver in a compensatory manner, thus improving the safety of hepatic resection and the resection rate of the tumor. Hemming et al. reported that preoperative portal vein embolization applied to patients whose liver tissue outside the lesion had not yet compensated for enlargement significantly reduced the incidence of postoperative complications. 2.2 Palliative surgery 2.2.1 Internal drainage of the intrahepatic bile duct intestinal drainage is the preferred option for patients with unresectable hilar cholangiocarcinoma at the time of surgery, and it can It can reduce the inconvenience and pain caused by long-term bile loss and bile duct infection. The following methods are commonly used: 2.2.1.1 Left intrahepatic bile duct jejunostomy The classic surgical method is the longmine procedure, however, this procedure requires resection of the left outer lobe of the liver and is very traumatic. 2.2.1.2 Right intrahepatic bile duct jejunostomy The origin of hilar cholangiocarcinoma is more on the left hepatic duct. Therefore, it is necessary to drain the right intrahepatic bile duct system to receive better results. In recent years, many scholars have adopted right hepatic duct, gallbladder and jejunostomy, which does not require separation of gallbladder and is less traumatic and simpler. 2.2.1.3 Intrahepatic support drainage This method is the preferred drainage method for patients with hilar cholangiocarcinoma who have lost the chance of surgical resection. In recent years, with the development of interventional technology, stents can be placed inside the bile duct through hepatic puncture for drainage or endoscopically into the bile duct for drainage, and the commonly used biliary stents are plastic and metal stents. Metal stents are more suitable for biliary tract malignancies because their surface can be covered by the biliary mucosa, which has the characteristics of preventing bacterial growth, long-lasting patency, and not easy to slip off. It can also be used for preoperative preparation. It is only necessary to cut the bile duct at the proximal end of the obstruction and place a drainage tube to drain the bile out of the body. This method is simple and can play the role of decompression and yellowing to a certain extent, but it is prone to water-electrolyte disorders and cannot achieve the purpose of prolonging survival and improving quality of life.2.3 In situ liver transplantation has the characteristics of intrahepatic metastasis, slow growth and late extrahepatic metastasis, so some scholars suggest that it can be a good indication for liver transplantation. The specific approach is to choose orthotopic liver transplantation (OLT), bile duct reconstruction, and Roux-Y anastomosis between the common bile duct and the recipient jejunum to maximize resection of the proximal bile duct and prevent recurrence. The indications for liver transplantation for hepatoportal cholangiocarcinoma are: ① patients who have been diagnosed with stage II of the International Union Against Cancer (UIcc) and cannot be resected by dissection; ② patients who are to be resected with R0 but can only be resected with R1 or R2 due to central tumor infiltration (R0 resection: no cancer cells at the cut edge; R1 resection: cancer cells visible microscopically at the cut edge; R2 resection: cancer cells visible visually at the cut edge); ③ patients with local recurrence in the liver after resection. In 1999-2003, Robles et al. performed total hepatectomy plus OLT in 36 patients with unresectable hilar cholangiocarcinoma, with survival rates of 82%, 53% and 30% at 1, 3 and 5 years after surgery, achieving similar outcomes as the radical resection group. If the lesion was less than 3 cm, the 5-year survival rate after liver transplantation was greater than 80%. However, it is still controversial whether to perform liver transplantation for hilar cholangiocarcinoma, and opponents believe that it is not worthwhile to spend a lot of labor and material resources and consume valuable donor liver resources just to achieve improved quality of life. In any case, OLT offers a broad prospect for the complete treatment of hilar cholangiocarcinoma.2.4 Combination therapy Combination therapy can be used as a stand-alone treatment, but it is mainly used as an adjunct to surgical treatment, which can effectively reduce the postoperative recurrence rate and improve the survival rate. In recent years, the main integrated treatment methods developed are neoadjuvant radiotherapy, gene therapy, etc. 2.4.1 Neoadjuvant radiotherapy is the first application of chemotherapy, followed by surgery, and then postoperative supplemented by chemotherapy and radiotherapy. The theory is that effective combination chemotherapy is applied before surgery to kill chemotherapy-sensitive tumor cells, followed by surgical resection of cancer foci and postoperative radiotherapy to destroy the remaining tumor cells in order to better control the tumor and reduce the chance of recurrence. Wiedmann et al. performed preoperative radiotherapy on 7 patients with hepatoportal cholangiocarcinoma, and the results showed that none of the cholangiocarcinoma cells remained under the biliary margin after surgery; while the residual rate of cancer cells in the biliary stump without preoperative radiotherapy was as high as 54% during the same period, suggesting that neoadjuvant radiotherapy can significantly improve the radical resection rate of surgery and reduce local recurrence.2. 4. 2 Gene therapy Oncology gene therapy is a promising biological Gene therapy is a promising biological treatment method. It is a method to inhibit or kill tumor cells directly or indirectly by introducing exogenous genes into human body. Commonly used gene therapy modalities include modification of tumor-related genes, immune gene therapy, suicide gene therapy and drug-resistant gene therapy. With the continuous maturation of theoretical and technical aspects of gene therapy, gene therapy has been widely used to treat liver cancer, pancreatic cancer, colon cancer, etc., but the treatment of hepatoportal cholangiocarcinoma is still at the stage of basic and animal experiments [25]. 2. 4. 3 Photodynamic therapy (photodynmnic therapy, PDT) is a local treatment method for tumors, which The retention rate of photosensitive drugs in tumor tissues is higher than that of normal tissues, and the laser irradiation of appropriate wavelengths causes cytotoxicity and other effects of photosensitive drugs, thus selectively killing tumor cells. In recent years, some scholars have used PDT to treat hepatoportal cholangiocarcinoma, which mainly consists of two parts: (1) firstly, intravenous injection of photosensitizing drug (hematoporphyrin derivative), which selectively enters the tumor tissue; (2) then irradiation of the tumor site with laser of appropriate wavelength through cholangioscope, which activates this complex and causes ischemic necrosis of tumor through direct cytotoxic effect and selective action on tumor microvasculature to achieve the effect of killing The effect is to kill cancer cells through direct cytotoxic effect and selective action on tumor microvasculature leading to ischemic necrosis. PDT can shrink the mass and restore bile drainage, thus improving patients’ quality of life and prolonging their survival. The average thickness of the tumor decreased from (8.7±3.7) mm to (5.8±2.0) mm after 3 months, and the quality of survival improved significantly with a mean survival of (558±179) d. The results were satisfactory.