Hepatoportal cholangiocarcinoma, also known as high-grade cholangiocarcinoma and Klastinoma, is a malignant tumor occurring in the left and right hepatic ducts and their confluence, and is the most common extrahepatic cholangiocarcinoma (accounting for 58%-75% of extrahepatic cholangiocarcinoma). In recent years, with the advancement and perfection of imaging and surgical techniques, the diagnosis and treatment of hilar cholangiocarcinoma have made great progress, and the clinical detection rate has significantly increased, and the surgical resection rate and postoperative survival rate have significantly improved. Surgical treatment of hepatoportal cholangiocarcinoma is one of the technical strengths of our department, which is briefly introduced as follows.
I. Clinical manifestations
There is no special clinical manifestation in the early stage of hepatoportal cholangiocarcinoma, but the common clinical manifestation is painless obstructive jaundice as the main manifestation, which is progressively aggravated and may be accompanied by symptoms such as hidden pain in the upper abdomen, poor appetite and weakness.
Second, clinical typing
The Bismuth staging is widely used in hepatobiliary surgery: type I tumor is located at the bifurcation of the common hepatic duct, and the left and right hepatic ducts are connected; type II tumor occupies the confluence of the left and right hepatic ducts, and there is no channel between them; type III tumor invades one hepatic duct, and type IIIa involves the right hepatic duct and type IIIb involves the left hepatic duct; type IV tumor involves both hepatic ducts.
Metastatic route
The metastatic pathways of hepatoportal cholangiocarcinoma include local infiltration, vascular invasion, lymphatic metastasis, nerve invasion and peritoneal implantation. Among them, nerve invasion and invasion to surrounding fibrous tissues can be considered as important features of cholangiocarcinoma metastasis, which is also the primary reason for the difficulty of eradication and high recurrence rate. Most cases of hilar cholangiocarcinoma have insidious clinical manifestation in early stage, and the tumor is infiltrating and jumping in growth, often involving nerve bundle membrane, invading blood vessels and liver tissues, and lymph node metastasis.
IV. Staging system
1.American Cancer Society extrahepatic cholangiocarcinoma staging system
Tis carcinoma in situ
T1: Histologically, the tumor is confined to the bile duct.
T2: tumor tumor invasion beyond the bile duct wall.
T3: tumor invades the liver, gallbladder, pancreas or unilateral portal vein branches or unilateral hepatic artery branches
T4: tumor invades any of the following sites: portal vein trunk, common hepatic artery or other adjacent tissues (colon, stomach, duodenum, abdominal wall).
N0: no regional lymph node metastasis. N1: with regional lymph node metastasis.
M0: no distant metastasis. M1: with distant metastasis.
Stage 0: carcinoma in situ
Stage I: Ia:T1N0M0, Ib:T2N0M0.
Stage II: Ⅱa:T3N0M0, Ⅱb: T1-3N1M0.
Stage III: locally invasive hard-to-resect tumor:T4 anyNM0
Stage IV: with distant metastasis i.e. any T, any N, M1.
2.Stage of bile duct cancer by International Union Against Cancer (UICC).
Stage 0: carcinoma in situ.
Stage I: tumor invades submucosa or muscle layer.
Stage II: Tumor invades the plasma membrane and surrounding connective tissue.
Stage III: The above with a lymph node metastasis.
Stage IV: Ⅳ tumor invades adjacent organs with or without lymph node metastasis; Ⅳb: the above with distant metastasis metastasis.
3.T-stage system of hepatoportal cholangiocarcinoma
T1: resectable tumor: tumor invading the bile duct confluence ± unilateral secondary bile duct root.
T2: potentially resectable tumor: tumor invades the confluent part of bile duct ± unilateral secondary bile duct root, and also invades ipsilateral portal vein ± ipsilateral hepatic lobe atrophy.
T3: unresectable tumor: tumor invades bile duct confluence ± bilateral secondary bile duct root; or tumor invades unilateral secondary bile duct root with contralateral portal vein; or tumor invades unilateral secondary hepatic duct root with contralateral hepatic lobe atrophy; or tumor invades main portal vein or bilateral portal vein branches.
V. Diagnosis
The diagnosis of hepatoportal cholangiocarcinoma mainly relies on imaging techniques, such as ultrasound, CT, MRI, PTC, ERCP and other imaging techniques. Magnetic resonance cholangiopancreaticography (MRCP) is the ideal non-invasive examination method at present, which can clearly and accurately show the location, scope and the upper and lower ends of obstruction of the hilar mass, and the accuracy rate of localization and qualitative diagnosis of hilar cholangiocarcinoma can reach almost 100%. MRCP has become the primary examination method after ultrasound initial screening, and has basically replaced diagnostic PTC and ERCP in clinical practice in the past 5 years. MRCP can also indicate whether there is portal vein invasion and whether there are metastases in the liver and surrounding lymph nodes, which provides a reliable basis for preoperative tumor resectability assessment.
A19-9 and CA242 have good sensitivity and specificity and can be used as one of the screening indicators for hilar cholangiocarcinoma. Therefore, bile duct cancer should be highly suspected when there are non-specific gastrointestinal symptoms, mild intrahepatic bile duct dilatation and abnormally elevated CA19-9 and CA242 detected by ultrasound.
VI. Treatment
The first choice of treatment for cholangiocarcinoma of the hepatic portal is surgical resection. In recent years, due to the advancement of diagnostic and treatment techniques and the treatment concept of actively striving for surgical resection, the level of surgical treatment has made great progress. Vascular skeletonization, combined hepatic lobectomy, expanded lymph node dissection and biliary tract reconstruction are the main aspects of radical surgery for hilar cholangiocarcinoma. If necessary, combined with various types of hepatic lobectomy and vascular resection techniques can improve the radical resection rate.
1.Surgical treatment
Radical surgery for hilar cholangiocarcinoma is the only treatment that can improve the long-term survival rate of patients after surgery. The standard of radical resection for hilar cholangiocarcinoma is to remove the whole tumor and its surrounding invaded liver, blood vessels, lymph and nerve tissues.
For cholangiocarcinoma of the hilar region with accumulated hepatic artery and portal vein, resection should still be actively pursued as long as radical treatment can be achieved. Local resection of the involved portal vein on the preserved liver side must be followed by reconstruction to ensure recovery of liver function. Some data show that the efficacy of lobectomy and extrahepatic cholangiocarcinoma plus reconstruction of invaded portal vein is close to that of lobectomy and extrahepatic cholangiocarcinoma alone without portal vein invasion. Some experimental studies have shown that after hepatic artery ligation and blockade, there is a short interruption of blood flow for 1-2 h. In the second hour, the arterial blood supply starts to recover, and in the 12th hour, the blood pressure before the blockade is reached. Therefore, it is believed that blocking the hepatic artery alone does not cause substantial damage to the hepatobiliary system. However, some scholars believe that in combined radical resection of hilar cholangiocarcinoma with lobectomy, the arterial traffic branches around the liver are mostly severed due to the clearance of the hilar region and the freeing of the liver, and the reconstruction of the traffic branches after severing the hepatic artery is completely different from the rapid recovery of the collateral circulation in the hilar region after simple hepatic artery ligation or embolization. Therefore, the degree of liver damage is more severe than that of general ligation and embolization, and the occurrence of serious complications after surgery will be greatly increased. Our experience supports the former view that reconstruction is not necessary after hepatic artery dissection, and liver function is affected in the early stage after hepatic artery dissection on the healthy side, but it can gradually return to normal after a period of time. Of course, the hepatic artery should be preserved as much as possible during the operation, unless it affects the radical effect of bile duct cancer.
2.Palliative surgery
The early bile duct mucosa of hepatoportal cholangiocarcinoma grows infiltratively to the proximal side of bile duct, invades the nerves, lymph and blood vessels of hepatoduodenal ligament, and metastasizes along the perineural space in the form of “jumping”, which can invade the high bile duct and hepatoportal tissue. The rate of resection is low, and the rate of radical resection is even lower, so palliative treatment is the only option at this time. The effective means of palliative care is to establish internal or external biliary drainage to relieve obstruction, mainly including bile-intestinal anastomosis, endobiliary stenting, endoscopic placement, PTCD, etc. It has been reported in the literature that the average survival of patients with unresectable hilar cholangiocarcinoma without effective biliary decompression and drainage treatment is only 3 months, and the cause of death is cholangitis and liver failure due to biliary obstruction rather than tumor spread, which also indicates the necessity of aggressive surgical treatment and the possibility of prolonging life. Palliative internal/external bile drainage can prolong the survival time (about 6-12 months) and improve the quality of life of patients with bile duct cancer.
3.Other palliative treatments
Clinical practice shows that cholangiocarcinoma of the hilar region is not sensitive to radiotherapy and chemotherapy, immunotherapy and traditional Chinese medicine conditioning are only of adjuvant therapeutic value, while internal and external biliary drainage combined with the above non-surgical treatments can effectively reduce yellowing and delay the progression of the disease in some cases, but there is continued growth of cancer foci and substantial deterioration of the overall condition.
Relevant literature views.
1.R0 resection is the key to improve prognosis
At present, surgical resection is still the only possible method to obtain hope of cure for hilar cholangiocarcinoma. With the development of hepatic resection technology, radical resection combined with lobectomy and extended radical resection are gradually and commonly carried out, the surgical resection rate is gradually improved, and the radical resection rate and survival rate are improved. In the past two decades, the domestic surgical resection rate has increased from 10% to 54.3%-83.3%, with the radical resection rate being about 30%-50%. The combined lobectomy rate in some medical centers in Japan is 60% to 90%. The radical resection rate of hepatoportal bile duct cancer is 50% to 80%, and the 5-year survival rate is 30% to 50%.
The surgical approach is classified according to the presence or absence of cancer cells at the cut edge as follows: 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. The statistics of hepatoportal cholangiocarcinoma in Lahey Center (100 cases) in the United States and Nagoya Center (155 cases) in Japan showed that the overall 5- and 10-year survival rates of patients were 7%, 0% and 16% and 12%, respectively, among which the 5- and 10-year survival rates of patients with R0 resection were 43%, 0% and 25% and 18%, respectively. In a retrospective analysis of 201 cases of hilar cholangiocarcinoma, the survival rates at 1, 3, and 5 years after surgery for the late 75 patients with R0 resection were 90%-91%, 40%-91%, and 13%-64%, respectively; whereas the survival rates for non-R0 resection were only 55%, 10%, and 0.
2.The status of combined hepatectomy in radical resection of hilar cholangiocarcinoma
Radical resection of tumor so that the cut margin is negative, only resection of tumor is usually not enough. Many clinical studies have shown that resection of tumor in the hilar region only often results in R1 or R2 resection with positive cut margin. In recent years, resection of biliary tumors along with partial hepatectomy has gained increasing acceptance. In order to achieve the standard of radical resection with no cancer within 5 mm of the incisional margin, partial hepatectomy is generally required for all types except type I and some type II, which can be performed only with hilar bile duct resection and lymphatic dissection.
According to the Bismuth classification of hilar cholangiocarcinoma, the following procedures are most reasonable for hilar cholangiocarcinoma: local resection of tumor for type I; type II can add caudal lobectomy or hepatic lobectomy on the basis of local resection; type IIIa local resection + left hepatectomy, type IIIb local resection + right hepatectomy or middle lobe resection; type IV can only choose palliative drainage or liver transplantation. Our department has been following the above principles to develop the surgical plan.
The basis of additional caudal lobe resection: cholangiocarcinoma in the hilar region has infiltrative growth, characterized by infiltration at the hepatic end is greater than that at the duodenal end, and infiltration at the submucosal layer is more than that at the mucosal layer, so it can easily infiltrate the caudal lobe bile duct. It can also invade the portal vein system and then spread to the caudate lobe via hematogenous dissemination. Surgical treatment of hilar cholangiocarcinoma is necessary to remove the caudate lobe of the liver. It is generally believed that portal cholangiocarcinoma mostly has caudate lobe infiltration, and caudate lobe resection is required for invasion of confluence or left and right hepatic ducts. Many scholars advocate that caudate lobectomy together with caudate lobe resection is to increase the thoroughness of surgery, but this view has not yet gained universal agreement. We add caudate lobectomy for type II or higher hilar cholangiocarcinoma.
3.The role of lymph node dissection in the radical treatment of hilar cholangiocarcinoma
Most hilar cholangiocarcinoma is adenocarcinoma, and the incidence of lymph node metastasis is 30% to 60%. Lymph node dissection is one of the most important measures to improve the curative effect. For the scope of lymph node dissection, the current mainstream view is that the lymph, nerve and fibro-adipose tissue on the hepatoduodenal ligament, including the skeletonization of the hepatic artery and portal vein, need to be removed in its entirety starting from the common hepatic artery. The need to clear the lymph nodes adjacent to the superior mesenteric artery and adjacent to the abdominal aorta is still controversial.
4.The role of vascular resection/reconstruction in the radical treatment of hilar cholangiocarcinoma
The distance between the bile ducts in the hilar region and the hepatic artery and portal vein is less than 2 mm on average, and vascular invasion is common. Infiltration of the hepatic artery or portal vein by cholangiocarcinoma of the hilar region was previously considered a contraindication to surgery. With the improvement of vascular surgery techniques, these contraindications have been broken down, and the infiltrating portal vein is removed together with the tumor, and techniques such as end-to-end anastomosis between the main trunk of the portal vein, between the left branch of the main trunk-portal vein, and reconstruction of the portal vein with an external iliac vein patch graft are applied for reconstruction.
On the one hand, combined portal vein resection can reduce the residual tumor cells and improve the radical resection rate; on the other hand, this procedure can avoid intraoperative touching and squeezing of the tumor and reduce the chance of metastasis, which is more in line with the principle of “tumor-free surgery”. The portal vein provides 70% to 75% of the blood supply to the liver and enters the liver, and its branches mainly nourish the hepatic parenchymal cells, so it plays a vital role in the maintenance and recovery of liver function. It is now accepted that the portal vein must be reconstructed after resection and that an adequate blood supply is preserved. Regarding the efficacy of portal vein resection and reconstruction, it has been suggested that portal vein resection can significantly improve the survival rate of patients with progressive hepatoportal cholangiocarcinoma. Moreover, portal vein resection reconstruction does not result in higher operative mortality and complication rates.
Combined hepatic artery resection for hilar cholangiocarcinoma is still controversial. The main issue is whether to reconstruct the hepatic artery after resection. Some scholars believe that reconstruction is not necessary after hepatic artery resection, on the grounds that there is a certain rate of complications such as anastomotic bleeding and thrombosis after arterial reconstruction, especially for those with large tumors that have encircled the hepatic artery, the hepatic artery may have been occluded and collateral circulation has been formed. However, for those whose arteries are only partially invaded, most scholars advocate reconstruction after hepatic artery resection. It is difficult to establish collateral circulation in the short term after hepatic artery dissection, and the intra- and extrahepatic bile ducts have to go through a longer period of ischemia. The literature reports that the incidence of postoperative biliary complications is 100% in those who have not reconstructed after hepatic artery resection, while the incidence of complications is only 20% in those who have reconstructed the artery. Therefore, immediate reconstruction after hepatic artery resection is of great importance to reduce the occurrence of complications after surgery.
5.The role of portal vein embolization in the radical treatment of hepatoportal cholangiocarcinoma
Radical surgery for hilar cholangiocarcinoma often requires combined lobectomy, and the functional capacity of the residual liver must be considered. Italian scholars have proposed to reduce the incidence of postoperative hepatic failure by preoperative portal vein embolization of the hemi-liver to be resected, which causes atrophy and compensatory hypertrophy of the preserved hemi-liver. Different studies have shown that 2 weeks after the implementation of portal vein embolization, the volume of the contralateral normal liver can increase by 9% to 25%. There is no international consensus on how small the residual liver should be before portal vein embolization of the affected liver is required, but it is generally believed that when the volume of the residual liver is 25% to 40% of the total liver volume, portal vein embolization can effectively reduce the incidence of postoperative liver failure. In a Japanese study, the incidence of postoperative liver failure was reduced from 33.3% to 23.8% in patients with most of the liver removed, and the perioperative mortality rate was reduced from 21.9% to 9.5% from 2001 to 1.6% at the time of reporting. However, the possible complications of portal vein embolization should also be seen, including ectopic embolization of the normal liver, intra-abdominal hemorrhage, biliary bleeding, tumor progression, and the possibility of uncompensated hypertrophy of the healthy liver. The overall incidence of the above complications has been variously reported to range from 7.5% to 14.8%. Even so, most surgeons in Japan still use preoperative PVE as a routine means at present.
6. Triple means in Japan
In order to achieve combined multi-segment liver and portal vein resection to increase radicality and reduce postoperative recurrence, and to prevent postoperative liver failure, Japanese scholars have proposed a triple means.
(1) drainage to reduce yellowness: drainage of the hepatic duct to reduce yellowness first, so that the blood bilirubin can be reduced to a lower level to eliminate the damage of obstructive jaundice to patients.
(2) Portal embolization: Embolization of the portal vein on the invaded and resected side of the liver for about 2 to 3 weeks to increase the hypertrophy of the liver on the preserved side to improve the hepatic reserve for combined resection of multiple liver segments.
(3) Surgical resection: cholangiocarcinoma of the porta hepatis combined with multiple hepatic segments and portal vein resection.
Japanese scholars reported the application of triple means to treat 79 cases of hilar cholangiocarcinoma, and the 5-year survival rate of R0 resection reached 40%.
7.Liver transplantation
This procedure is still controversial. Opponents believe that it is not worthwhile to spend a lot of human and material resources, as well as precious donor liver resources, just to improve the quality of life. Advocates believe that hilar cholangiocarcinoma is a good candidate for liver transplantation because of its intrahepatic metastasis, slow growth and late extrahepatic metastasis. The indications for liver transplantation for hilar cholangiocarcinoma proposed by some people are: (1) patients who have been diagnosed as stage II patients and cannot be resected by open exploration; (2) patients who are to be resected by R0 but can only be resected by R1 or R2 due to central tumor infiltration; (3) patients with local recurrence in the liver after surgery.