Hepatoportal cholangiocarcinoma is mainly local infiltration, and because of its special location and anatomical relationship of the hilar region, it is very easy to invade the liver parenchyma and the vascular nerves of the hilar region, so the surgical resection rate is low and the prognosis is poor. In recent years, with the maturity of surgical techniques, combined lobectomy has been gradually applied to the treatment of hilar cholangiocarcinoma, so that the resection rate of hilar cholangiocarcinoma has been improved more obviously [1-3]. In this paper, we summarized the clinical and follow-up data of 67 cases of resected hilar cholangiocarcinoma treated in the same surgical group from June 2005 to October 2008 in Henan Provincial Cancer Hospital, and discussed the clinical value of lobectomy in the treatment of hilar cholangiocarcinoma. Zhou Jinxue, Department of Hepatobiliary and Pancreatic Surgery, Henan Cancer Hospital
Data and Methods
1.General information
From June 2005 to October 2008, 67 patients with hepatoportal cholangiocarcinoma were treated by surgical resection in the surgical group of the author. There were 41 male cases and 26 female cases. The age ranged from 47 to 81 years old, with a mean age of 63.6 years. The preoperative serum total bilirubin ranged from 73.8 to 643.6 μmol/L, with a mean of 321.2 μmol/L. The clinical manifestations mainly included generalized skin and sclera yellowing, epigastric pain and discomfort, abdominal distension, poor appetite, and weight loss. Preoperative ultrasound, CT or MRI were routinely performed, and no PTCD or endoscopic tube placement was performed to reduce yellowing.
2. Surgical methods
The resectability of hepatoportal cholangiocarcinoma and the choice of surgical approach mainly depend on the surgical exploration. There are two key steps in this operation: one is the anatomical separation of the hepatic hilar plate; the other is the transection of the common bile duct and traction upward to the hepatic hilum to investigate whether there is vascular invasion of the tumor and its degree and scope. If necessary, the square lobe of the liver can be resected to expose the porta hepatis, so that the dilated primary and secondary bile ducts above the tumor can be easily found and confirmed by fine needle aspiration.
The basic procedure includes extrahepatic bile duct, cholecystectomy, vascular skeletonization of the hepatoduodenal ligament and extensive resection of lymphatic, fatty and neural tissues in the hepatoduodenal ligament (Figure 1), and biliary-intestinal anastomosis. The decision to resect the liver is based on the extent of the bile duct tumor and the preoperative functional reserve of the liver, and the intraoperative liver resection can be individualized according to the specific situation. Some type IV cholangiocarcinoma had additional hepatic hemicolectomy and caudate lobe resection on one side depending on the invasion of the hilar bile duct. After shaping the bile ducts in the hilar region, Roux-en-Y anastomosis was made with the jejunum (Figure 4). If the tumor invades the lower part of the common bile duct, it is combined with pancreatic head and duodenum resection. If the hepatic artery is invaded, the hepatic artery is resected directly without reconstruction; if the portal vein and hepatic artery are invaded at the same time, the hepatic artery is resected first, and depending on the invasion of the portal vein, wedge resection of the portal vein, segmental resection, and repair or reconstruction can be performed respectively. According to whether the hepatic lobectomy was attached or not, the group was divided into combined hepatectomy group and uncombined hepatectomy group.
Figure 1 Bile duct resection with hepatoduodenal skeletal floral clearance Figure 2 Combined right hemicolectomy and caudate lobectomy, with the left bile duct in the clamp site
Figure 3 Combined right hemicolectomy and caudate lobectomy Figure 4 Roux-en-Y with jejunum after bile duct revision
Roux-en-Y resection of the bile duct, with the right side of the bile duct at the site of clamping Anastomosis
3. Follow-up and statistical analysis
The starting point of prognostic observation was the day of surgery, and postoperative complications and regressions were recorded in a timely manner. Patients were followed up by telephone or outpatient after presentation. The cumulative survival rate was calculated using the SPSS 12.0 software Kaplan-Meier. Log-rank test was used for comparison of survival data, and P<< span="">0.05 was considered a significant difference.
Results
1. Bismuth staging and surgical approach for hilar cholangiocarcinoma (Table 1)
The surgical approach was performed according to intraoperative exploration and Bismuth clinical staging. 38 cases were combined hepatectomy and 29 cases were not combined hepatectomy, and 1 case was combined pancreaticoduodenectomy; 51 cases were combined hepatic artery resection according to the vascular invasion. There were 3 cases of direct repair of portal vein wedge resection, 2 cases of portal vein segmental resection, including 1 case of direct anastomosis and 1 case of autologous saphenous vein graft.
Table 1 Bismuth typing and surgical methods of hepatoportal cholangiocarcinoma
Bismuth typing Type I Type II Type IIIa Type IIIb Type IV
Hepatectomy group 0 8(3)# 4(1)# 7(5#) 19(13)#
Non-hepatectomized group 3 4 0 0 22
Total number 3 12 4 7 41
# The number of cases with additional caudate lobectomy is in parentheses
2. Pathological types and cut margins
The pathology of the group was confirmed as bile duct cancer, including 61 cases of adenocarcinoma, 1 case of papillary adenocarcinoma, 2 cases of adenosquamous carcinoma, 2 cases of squamous carcinoma, and 1 case of undifferentiated carcinoma. The degree of radical tumor treatment was divided into R0 radical treatment (negative bile duct margin), R1 radical treatment (negative biliary margin, positive pathology) and R2 radical treatment (positive biliary margin) according to the results of bile duct margin cutting. There were 21 cases of R0 radical treatment in the hepatectomy group, 17 cases of R1-R2 radical treatment, and 55.3% of R0 radical treatment; 10 cases of R0 radical treatment in the group without hepatectomy, 19 cases of R1-R2 radical treatment, and 34.5% of R0 radical treatment. there was a difference between the two groups in the R0 radical treatment rate (P < 0.05).
3. Postoperative complications
Complications occurred in 15 cases in the hepatectomy group, with an incidence of 39.5%, including 4 cases of pleural effusion, 1 case of incisional infection, 1 case of upper gastrointestinal bleeding, 4 cases of bile leak, 1 case of hepatic trauma bleeding, 2 cases of subphrenic fluid infection, 1 case of pulmonary infection, and 1 case of death from hepatic and renal failure. Complications occurred in 4 cases in the unincised liver group, with an incidence of 13.8%, 3 cases of biliary leakage and 1 case of biliary bleeding. There was a significant difference in the incidence of complications between the two groups (P < 0.01).
2.4 Follow-up
A total of 58 cases were effectively followed up, with a total follow-up rate of 86.6%. The cumulative survival rates at 1, 3, and 5 years were 76.7%, 41.4%, and 20.7%, respectively, calculated by Kaplan-Meier for the whole group. The cumulative survival rates at 1, 3, and 5 years were 89.3%, 53.6%, and 32.1% for the entire group of 31 patients treated with R0 root, and 69.7%, 30%, and 10% for the R1~R2 root group at 1, 3, and 5 years, respectively, with significant differences in postoperative survival rates between the two groups (P < 0.05, Figure 5). The cumulative survival rates at 1, 3, and 5 years were 81.8%, 48.5%, and 24.2% in the hepatectomy group and 75%, 32%, and 16% in the unhepatectomized group at 1, 3, and 5 years, respectively, and there was a statistically insignificant difference in postoperative survival rates over time between the hepatectomized and unhepatectomized groups (P < 0.05, Figure 6).
Figure 5 Survival curves of R0 versus R1~R2 radical treatment groups Figure 6 Survival curves of hepatectomy versus non-hepatectomy groups
Discussion
1. The necessity of hepatic resection in radical surgery for hilar cholangiocarcinoma
Radical resection of hepatoportal cholangiocarcinoma is the key to improve the long-term survival rate of patients at this stage. Due to its special anatomical location and unique biological behavior, hilar cholangiocarcinoma mostly invades the proximal bile ducts and intrahepatic bile ducts along the submucosa of bile ducts, and easily invades the liver parenchyma around the hilar, and can metastasize to the liver via peribiliary lymphatic, requiring partial hepatic resection in 50% to 100% of cases [4-6]. completed tumor resection, among which 40 cases were combined with lobectomy, accounting for 93% of the resection group, and the R0 radical cure rate was 77%. According to Huang [8], combined lobectomy for hilar cholangiocarcinoma is a key step to improve the rate and completeness of tumor resection.
In the treatment of hilar cholangiocarcinoma, negative margins should be sought first, including intraoperative margin cryopathology, and the treatment effect of negative margins (R0) is significantly better than that of palliative resection (R1~R2). In high Bismuth staged hilar cholangiocarcinoma, R0 radical treatment could not be achieved by extrahepatic choledochotomy alone, and additional lobectomy could improve the radical resection rate. A group of 79 resected cases of hilar cholangiocarcinoma reported that the 1-, 3-, and 5-year survival rates were 90.4%, 52%, and 39.9% for those with negative cut-off margin histology, compared with 87.1%, 24.2%, and 6% for those with positive margins, indicating that negative cut-off margins significantly affect prognosis [9]. In this study, the R0 cure rate was 55.3% in the hepatectomy group and 34.5% in the group without hepatectomy, and the R0 cure rate was significantly higher in the hepatectomy group than in the group without hepatectomy; the cumulative survival rates at 1, 3, and 5 years were 83.4%, 51.2%, and 22.3% for all 31 cases with R0 cure, respectively, which were significantly different from the postoperative survival rates of patients with R1~R2 cure. Therefore, for Bismuth type III or IV cases, resection of hilar cholangiocarcinoma with additional liver resection is the first choice, while local resection should not be chosen when radical surgery is proposed. It seems indisputable that to improve the long-term survival rate of hilar cholangiocarcinoma, the scope of surgery must be expanded to increase the surgical thoroughness [10,11]. In addition, a parallel relationship between negative margins and hepatic resection volume has been demonstrated [12], and combined lobectomy not only improves the R0 radical resection rate, but also improves tumor-free survival and reduces the incidence of liver metastases [1,13].
The left and right caudal lobe bile ducts both open directly at the confluence of the left and right hepatic ducts and the common hepatic duct, and as many as 31%-98% of cholangiocarcinomas in the hilar region invade the caudal lobe, which is also a common site of recurrence [4]. Therefore, most scholars believe that surgery combined with caudate lobe resection is necessary, and this has led to better clinical outcomes. Gazzaniga et al[14] reported that the 5-year survival rate of patients with combined caudate lobectomy was 25%, while the 5-year survival rate of those without it was 0.
2. Evaluation of tumor resectability
Ultrasound can be the first choice, and the Bismuth staging rate for hilar cholangiocarcinoma is 71%-92%, which can provide a basis for preoperative evaluation; CT can determine the exact location and size of tumor invasion in the liver and the situation of portal vein invasion. The preoperative magnetic resonance cholangiopancreaticography (MRCP) has an accuracy rate of 100% in localizing hilar cholangiocarcinoma, a correct rate of 89% in identifying the extent of tumor, and a correct diagnosis rate of 75%-91%.
In view of the objective limitations of preoperative imaging results and the differences in the interpretation of examination results, a comprehensive and detailed intraoperative exploration should be performed to make an accurate assessment of the extent of tumor infiltration, the degree of liver siltation and sclerosis, the part and extent of vascular infiltration, and the presence or absence of metastasis, in order to determine a safe and reasonable scope of surgical resection [16].
3.Management of vascular invasion
Vascular invasion is a sign of intrahepatic infiltration and spread of hilar cholangiocarcinoma tumor, especially portal vein invasion is one of the main reasons for unresectable hilar cholangiocarcinoma[17] .Hemming et al[18] reviewed 60 cases of hilar cholangiocarcinoma combined with portal vein resection, and the operative mortality rate in the portal vein resected group (4%) was comparable to that in the unresected group (12%), while the negative margin rate reached 80%. Therefore, portal vein resection is considered safe and feasible for radical resection of hilar cholangiocarcinoma.
In our opinion, we do not perform portal vein resection even if the portal vein is infiltrated on preoperative imaging and can be separated from the tumor intraoperatively. On the contrary, even if the infiltration of portal vein is not found in the preoperative examination, but cannot be separated from the tumor intraoperatively, portal vein resection should be performed. When dealing with the involved vessels, the proximal and distal ends of the involved vessels should be fully separated first, and the length of the involved vessels should be clarified to decide whether to perform wedge resection or segmental resection, and if necessary, patching or vascular grafting [19]. When reconstructing the portal vein, it should be noted that: 5-0 or 6-0 prolene non-invasive vascular sutures are generally used for the anastomosis, either continuous or interrupted sutures, and the time to block the portal vein should not be too long, and should be completed in about 25 min; the circumference of the portal vein should not be less than 1/3 of the original circumference after wedge resection anastomosis; there should be no tension at the anastomosis during segmental anastomosis. When the hepatic artery is invaded and resected, we generally do not advocate reconstruction as long as the blood supply of the preserved lateral portal vein is good [20,21].
4.Pay attention to perioperative management
Hepatoportal cholangiocarcinoma mostly causes a series of pathophysiological changes due to obstructive jaundice, especially additional liver resection increases the surgical trauma and risks, and the surgical complications are significantly higher than those in the uncut liver group. In this study, there were 15 cases of complications in the hepatectomy group, with an incidence of 39.5%, including one case of death due to liver and kidney failure, which was significantly higher than that in the unincisional group (13.8%). Active and proper perioperative management and skillful surgical technique are the keys to reduce postoperative complications and decrease surgical mortality [22]. Perioperative management includes correction of hypoproteinemia and electrolyte disorders, emphasis on maintenance of liver and kidney function, prevention and treatment of infection, strengthening nutritional support, and reducing surgical bleeding and operative time.