One, treatment
1. The current most effective method for the surgical treatment of hilar bile duct cancer is still surgical resection. However, the biological behavior of bile duct cancer determines its low resection rate in clinical features, especially hilar bile duct cancer. Due to its location outside the bile duct and a special site, it is often diagnosed at an advanced stage once diagnosed, so the difficulty of surgical resection is greater. Literature reports indicate that about 5% to 50% of bile duct cancers can be surgically resected, with an average of 20%.
(1) Preoperative preparation: Due to the extensive range of liver hilum bile duct cancer resection surgery, in many cases, it is necessary to perform liver lobectomy at the same time, and patients often have severe jaundice, malnutrition, and low immunity. In addition, bile duct cancer patients are generally older, so good preoperative preparation is very important.
① General preparation: Systematic laboratory and imaging examinations to understand the overall condition, supplement the physiological needs of water, electrolytes, etc., and use antimicrobial drugs before and during surgery. It is necessary to confirm before surgery whether the cardiovascular and respiratory function can withstand the surgery. Mild cardiovascular and respiratory function impairment should be corrected before surgery, and coagulation dysfunction should also be corrected as much as possible before surgery.
② Liver protection treatment: For patients with long-term severe jaundice, especially those who may undergo extensive liver, bile, and pancreas resection surgery, the evaluation of liver function and liver protection treatment before surgery is very important. Some lesions can be resected locally, but due to insufficient liver reserve, it is difficult to withstand the surgery and lose the opportunity for surgery. Patients with sufficient preoperative preparation can still go through the perioperative period smoothly, even if the surgery is complex, time-consuming, and extensive. Preoperative preparation is the premise of ensuring the safety of surgery implementation and reducing complications, and reducing mortality. The following situations indicate poor liver function and are not suitable for combined liver surgery, especially禁忌 half-liver or above liver or pancreas resection surgery: A, serum total bilirubin above 256μmol/L; B, human serum albumin below 35g/L; C, prothrombin activity below 60%, with an extended time greater than 6s, and it is still difficult to correct after one week of vitamin K1 injection.
The indigocyanine green perfusion test (indigocyanine green test) is abnormal. CT is used before surgery to measure the total liver volume, plan the volume of liver to be resected, and calculate the volume of liver to be preserved, which is helpful for the evaluation of liver function for the planned extended hepatic hilum bile duct cancer radical resection. In addition, the glucose tolerance test, the determination of prealbumin, and other tests are helpful for estimating the patient's liver function. Liver protection treatment before surgery is necessary. However, if biliary obstruction cannot be relieved, relying solely on drug liver protection is not effective. The purpose of the commonly used drugs is to reduce transaminases, supplement energy, increase nutrition, commonly use hypertonic glucose, human serum albumin, branched-chain amino acids, glucuronic acid, coenzyme Q10, vitamin K, and high-dose vitamin C, etc. Liver protection treatment before surgery should also pay attention to avoid using drugs that are harmful to the liver.
④Nutritional support: Providing appropriate nutritional support before surgery can improve the patient's nutritional status, reduce postoperative complications. Studies have shown that parenteral nutrition can increase the total number of lymphocytes, improve the immune mechanism, defend against infection, promote wound healing. It is currently recognized that perioperative nutritional support has a definite effect on reducing the incidence of complications and mortality, and promoting patient recovery. For general patients, peripheral venous nutrition can be adopted; for severe patients or those expected to have larger surgeries, a central venous catheter can be placed 5 to 7 days before surgery. For patients with mild liver damage, the energy supply during nutritional support should be 2000 to 2500 kcal/d, protein 1.0 to 1.5 g/(kg·d), with sugar accounting for 60% to 70% of non-protein calories, and fat accounting for 30% to 40%. When blood glucose is high, exogenous insulin can be administered. For patients with liver cirrhosis, the energy supply should be 1500 to 2000 kcal/d. When there is no hepatic encephalopathy, the protein dosage should be 1.0 to 1.5 g/(kg·d); when there is hepatic encephalopathy, protein intake should be limited, based on the condition, to 30 to 40 g/d, and 37% to 50% of branched-chain amino acids can be administered to provide energy, increase the ratio of branched-chain amino acids to aromatic amino acids in the blood, achieving the dual purpose of nutritional support and liver disease treatment. The dosage of branched-chain amino acids is 1 g/(kg·d), and fat is 0.5 to 1.0 g/(kg·d). In addition, sufficient vitamins and trace elements must be supplied. For patients with obstructive jaundice, the energy supply should be 25 to 30 kcal/(kg·d), sugar 4 to 5 g/(kg·d), protein 1.5 to 2.0 g/(kg·d), and fat should be limited to 0.5 to 1.0 g/(kg·d). The fat preparation given should be a mixture of medium-chain and long-chain fats, and sufficient vitamins, especially fat-soluble vitamins, must be provided. If the serum bilirubin level is >256 μmol/L, biliary drainage can be performed to配合 nutritional support. Preoperative jaundice reduction: There is still controversy about whether to reduce jaundice before surgery, and the reasons not to advocate for jaundice reduction are: A, the mortality and incidence of complications after reduction of jaundice have not been reduced; B, percutaneous transhepatic biliary drainage (PTCD) via endoscopic nasobiliary drainage (ENBD) is difficult to succeed; C, the complications, especially the threat of occlusive biliary tract infection, are significant with percutaneous liver puncture and external biliary drainage (PTCD).
The reasons for advocating bile drainage are as follows: A, Good preoperative preparation is necessary for extensive radical resection, and bile drainage is very necessary; B, Preoperative decompression for 3 weeks is better than 1 week or 2 weeks; C, There is a significant improvement in the function of the endothelial system and coagulation function; D, At the cellular level, such as prostaglandin metabolism, it is conducive to alleviating liver damage; E, It is conducive to the safety of large liver resection. In China, it is generally believed that for cases with total serum bilirubin higher than 256μmol/L, bile drainage and drainage are often adopted before the implementation of large radical surgery or large liver resection. It is generally believed that for severe jaundice, long duration (more than 1 month), poor liver function, and the need for major surgery, preoperative bile drainage and drainage are beneficial and necessary. If bile drainage and drainage are effective but the overall condition has not been significantly improved, and the recovery of liver function is not ideal, the decision to undergo major surgery should also be made cautiously. Some foreign researchers, while achieving successful bile drainage, use interventional embolization of the patent portal vein on the diseased side to promote atrophy of the diseased liver and proliferation of the healthy liver, which is both conducive to surgery and conducive to reducing postoperative complications of poor liver compensation. This can be taken as a reference.
⑤Judging the possibility of resection of the lesion: It is an important link in the preoperative preparation of hilar bile duct cancer, which is conducive to formulating feasible surgical plans, reducing blindness, and is mainly determined by imaging examinations. However, it is very difficult to achieve accurate judgment before surgery, and sometimes it is necessary to perform laparotomy and exploration to confirm it. Therefore, it should be emphasized that various examination methods complement each other. For the judgment of the possibility of bile duct cancer resection, it is generally estimated preliminarily based on preoperative PTC, CT, and SCAG, but ultimately it still depends on the findings during surgery and intraoperative ultrasound. Intraoperative percutaneous liver puncture cholangiography can also be used for judgment. Some authors propose that bile duct cancer with the following conditions has the possibility of resection:
A. The portal vein is not involved by the tumor.
B. The portal vein and hepatic artery on the non-tumor side are not involved by the tumor.
C. There should be a sufficient length of normal common bile duct at the distal end, in order to resect.
D. At least one side of the bile duct has a normal secondary branch joint.
If imaging examination shows that the tumor involves 4 or more hepatic segment bile ducts, the possibility of resection is zero; if the involved bile duct is below 3 hepatic segments, there is about a 50% possibility of resection; if it only involves one hepatic segment bile duct, the resection rate may reach 83%; if the hepatic artery, superior mesenteric artery, or portal vein is involved, the resection rate is still 35%, but if the blood vessels are completely occluded, the resection rate is zero. The following situations should be considered as contraindications for surgical resection: A. Peritoneal implantation and metastasis; B. Generalized lymph node metastasis at the porta hepatis; C. Bilateral intrahepatic metastasis; D. Bilateral invasion of 2 or more hepatic ducts; E. Involvement of the proper hepatic artery or right and left hepatic arteries simultaneously; F. Direct invasion and wrapping of the main portal vein or portal vein trunk by the tumor.
⑥ The following situations are not suitable for radical resection:
A. Local tumor metastasis, such as tumor metastasis nodules on the peritoneal surface or omentum.
B. Involvement of the extrahepatic bile ducts outside the liver and duodenum ligament.
C. Angiography shows involvement of both main portal veins.
(2) Surgical methods: The surgical approach for bile duct cancer resection generally varies according to the location and classification of the tumor. Based on the Bismuth-Corlette clinical classification, for type I tumors, resection of the tumor and extrahepatic bile duct (including low position transection of the common bile duct, resection of the gallbladder, and clearance of the porta hepatis lymph nodes) can be adopted; for type II, resection of the tumor and caudate lobe resection is performed, and for the sake of better visibility, the liver quadrilateral lobe can be resected, and the rest is the same as type I; for type IIIa, the right half liver should be resected simultaneously based on the above; for type IIIb, the left half liver should be resected simultaneously; for type IV, the tumor invasion range is wide, the resection difficulty is great, and it can be considered to perform total liver resection and liver transplantation. The caudate lobe is located behind the first porta hepatis, its bile duct is short, and it is close to the bile duct convergence part near the porta hepatis. The two branches of the caudate lobe bile ducts respectively enter the right and left bile ducts or the left bile duct and the left posterior bile duct. The distant metastasis of bile duct cancer at the porta hepatis occurs late, but the infiltration and diffusion along the bile duct and peribiliary tissues is very common. Bile duct cancer that invades above the convergence part of the bile ducts can possibly invade the caudate lobe bile ducts and liver tissue. One group of reports showed that it accounted for 97%, therefore, caudate lobe resection should be an important part of radical resection of porta hepatis bile duct cancer. Bile duct cancer cells can directly infiltrate or can be transferred through blood vessels, lymphatic vessels, or through perineural spaces to the extrahepatic bile ducts and the connective tissue of the hepatoduodenal ligament. Therefore, careful dissection, resection of the porta hepatis nerve fibers and plexus, and sometimes even including the right lumbar plexus, should be one of the basic requirements for radical resection of bile duct cancer. At the same time, it is as thorough as possible to clear the connective tissue and adipose lymphatic tissue within the hepatoduodenal ligament, achieving the 'skeletonization' of the blood vessels in the porta hepatis. In recent years, the surgical resection rate of porta hepatis bile duct cancer has increased significantly, and the resection rate has increased from the past 10% to about 50%.
①Incision: The right subcostal oblique incision or the upper abdominal hip roof incision is often used to obtain better exposure.
②Exploration: Cut the round ligament of the liver, systematically explore the abdominal cavity, determine the extent of the lesion. If there is peritoneal implantation and metastasis or extensive metastasis, radical surgery is no longer possible, and it should not be forced. If necessary, take a biopsy of the suspected lesion for frozen section pathological examination. The exploration of the porta hepatis tumor can be opened upwards to separate the liver quadrate lobe, separate the porta hepatis plate, enter the porta hepatis transverse groove and separate to both sides, which can generally be found in the hard nodule deep in the groove, which is relatively fixed and often extends towards the liver. At this time, attention should be paid to check the involvement of the right and left hepatic ducts. Subsequently, the operator inserts the index finger or middle finger of the left hand into the lesser omentum, with the thumb in front of the porta hepatis, to touch the entire extrahepatic bile duct, hepatic artery, and main portal vein to understand the situation of tumor invasion of blood vessels. It can be combined with intraoperative ultrasound, intraoperative angiography, etc., and compared with preoperative imaging data for further understanding of tumor grading, typing, and staging. According to the exploration results, adjust or change the preoperative planned surgical method.
③Excision of type I bile duct cancer: After deciding to perform tumor resection, first dissect the tissues within the porta hepatis, incise the peritoneum in front of the porta hepatis by adhering to the superior part of the duodenum, and separate the extrahepatic bile duct located in the right anterior position. Then dissect and separate the proper hepatic artery and its branches, and dissect and separate the portal vein trunk located at the back. After separating the three tubes, they are all pulled apart with thin silicone tubes. Then dissect the Calot triangle, cut and ligate the cystic artery, and separate the gallbladder from the gallbladder bed. The cystic duct can be temporarily not cut.
Cut the common bile duct above or below the duodenum, tie off the distal end; use the proximal part of the common bile duct as a牵引, and lift the common bile duct and lymph, fat, nerve, and fibrous tissue within the hepatoduodenal ligament upward, separating them from the portal vein and hepatic artery until above the tumor at the hepatic hilum. At this point, the hepatoduodenal ligament has reached the 'skeletonization' stage, and sometimes it is necessary to expose the confluence of the left and right hepatic ducts and separate them from the bifurcation part of the posterior portal vein. Then, cut off the proximal bile duct about 1.0 cm from the superior margin of the tumor, remove the specimen, and send it for pathological examination. If there is residual cancer at the upper edge of the bile duct, you should expand the resection range. If there is no residual cancer at the margin, if the tension of the bile duct anastomosis is not great, you can directly perform the bile duct end-to-end anastomosis; however, the common bile duct is usually cut very low, and direct anastomosis is often difficult, so it is better to perform a high bile duct and jejunoileal Roux-en-Y anastomosis.
④ Resection of type II bile duct cancer: After determining that the tumor can be resected, proceed according to the relevant steps for type I hilar bile duct cancer, then dissect and separate the hepatic portal plate, pull the gallbladder and common bile duct downward, use an S-shaped retractor to pull open the inferior margin of the hepatic quadrate lobe, and cut off the liver tissue bridge between the left and right lobes of the liver to expose the superior edge of the hepatic portal sulcus. If the bile duct cancer is localized and does not require lobectomy, you can cut the hepatic capsule along the anterior edge of the portal, separate the liver substance from the portal plate downward, lower the portal plate, and at this time, the confluence of the left and right hepatic ducts and the left and right hepatic ducts have been exposed. If the confluence of the bile duct or the left and right hepatic ducts are not well exposed, you can cut off part of the hepatic quadrate lobe before resecting the bile duct tumor.
The extent of the caudate lobe resection and the site of resection depend on the infiltrative range of the tumor. Most emphasize complete resection, and routine placement of occlusion bands at the upper and lower segments of the liver and inferior vena cava at the first hepatic portal to prevent fierce hemorrhage from the portal vein and inferior vena cava. There are three approaches for caudate lobe resection: left, middle, and right. The left (lesser omentum) approach involves a thorough transection of the gastrohepatic ligament, flipping the liver to the right to expose the left margin of the inferior vena cava; the right approach involves freeing the right half of the liver, flipping it to the left, and exposing the posterior inferior vena cava throughout; the central approach involves cutting through the liver substance along the median fissure to reach the hepatic hilum, then combining the left and right approaches to completely resect the caudate lobe. It is necessary to thoroughly free the liver, flip the right half and caudate lobe to the left, separate the loose connective tissue between the caudate lobe and inferior vena cava, and you can see a variable number of short hepatic veins. The distal ends of the short hepatic veins close to the inferior vena cava should be clamped or ligated with a thread first, then cut off. For a few patients, the ligation of short hepatic veins can also be performed through the left approach. Then, under the inferior edge of the transverse sulcus of the first hepatic portal, cut the hepatic capsule to expose and separate the Glisson structures leading to the caudate lobe, tie off the proximal end, and burn the distal end. When going through the central approach, after the short hepatic veins are transected, you can start to cut through the median fissure of the liver to reach the first hepatic portal, clearly exposing the left and right hepatic pedicles. At this point, you can free and tie off the Glisson system structures leading to the caudate lobe one by one, transect the connection between the caudate lobe and the left and right liver lobes, and resect the caudate lobe.
After the left and right bile ducts are separated, they are cut above 1.0 cm from the tumor, and after completing the tumor resection, the ends of the left and right bile ducts are shaped. The posterior walls of the adjacent left and right liver gallbladder orifices can be sutured separately to form larger orifices, and the left and right bile ducts are anastomosed with the jejunum by Roux-en-Y anastomosis. An internal stent may be placed for drainage if necessary.
⑤ Resection of type Ⅲ bile duct cancer: If the distance of invasion of the left and right bile ducts in the intrapulmonary part of type Ⅲ bile duct cancer is short and there is no need for hemihepatectomy, the surgical method is similar to type Ⅱ, but most type Ⅲ bile duct cancers invade the secondary branches of the left and right bile ducts or the liver parenchyma, and it is necessary to perform right hemihepatectomy (type Ⅲa) or left hemihepatectomy (type Ⅲb) to ensure the thoroughness of radical resection.
The treatment of type Ⅲa bile duct cancer: A, free the common bile duct and portal bile ducts at the hilum as in the methods for types Ⅰ and Ⅱ; B, cut the left hepatic duct above 1.0 cm from the tumor; C, preserve the left branch of the hepatic artery, cut and ligate at the origin of the right hepatic artery; D, separate the tumor from the anterior wall of the portal vein, ligate and suture close, and then cut; preserve the left branch of the portal vein; E, dissect the right perihilar ligament, free the right liver, separate the right hepatic vein, and ligate at its root; F, flip the right liver medially to expose the short hepatic veins between the caudate lobe and inferior vena cava, and ligate and cut them separately; G, block the first hepatic portal and perform a regular right trilobectomy.
The treatment of type Ⅲb bile duct cancer corresponds to that of type Ⅲa. The right branch of the hepatic artery and portal vein is ligated and cut at the beginning, the left hepatic artery and left portal vein trunk are ligated and cut near the common trunk of the left hepatic and middle hepatic veins, the left half liver is freed, the caudate lobe is resected via the left approach, the liver is flipped to the right, ligated and cut, the branches of the short hepatic veins are ligated and cut, and then the first hepatic portal is blocked for left hemihepatectomy.
After hemihepatectomy, the remaining lower half of the liver may still have left or right bile ducts, which can be anastomosed with the jejunum. Sometimes, the primary bile duct of the remaining lower half of the liver has also been resected, and there may be several small bile duct orifices on the liver section, which can be shaped and anastomosed with the jejunum. For those that cannot be shaped, part of the liver parenchyma can be scraped between the two small bile ducts to communicate the two orifices into a depression, and then anastomosed with the jejunum; if there are many orifices and it is difficult to communicate, and the orifices are small, unable to anastomose one by one, then part of the liver tissue around them can be scraped to form a concave area with multiple bile duct orifices, and then anastomosed with the jejunum.
⑥ Paliative resection of type Ⅳ bile duct cancer: The operation method can be divided according to whether there is residual cancer cell at the edge of tumor resection: R0 resection - no cancer cells at the edge, R1 resection - cancer cells can be seen under the microscope at the edge, R2 resection - cancer tissue can be seen with the naked eye at the edge. The surgical resection of malignant tumors should strive for R0, but the extensive infiltration of type Ⅳ hilar bile duct cancer makes R0 resection unrealistic. In the past, such patients were often only treated with drainage surgery. The current view holds that even if radical resection cannot be achieved, the survival rate of palliative resection is still significantly higher than that of simple drainage surgery. Therefore, as long as there is a possibility of resection, palliative resection of the tumor should be strived for. If bile duct drainage cannot be completed, resection surgery should not be performed again. When palliative resection is performed, it is often combined with liver quadrilateral lobe resection or the resection of the Ⅳth liver segment. If the bile duct on the left and right liver断面can be anastomosed with the jejunum, Roux-en-Y anastomosis should be performed. If anastomosis cannot be performed or it is only R2 resection, it should be inserted into the intrahepatic bile duct for external drainage, or the other end of the tube should be placed into the jejunum to become an internal drainage bridge between the bile duct and the jejunum. However, special attention should be paid to the prevention and treatment of retrograde cholangitis.
⑦ Treatment of adjacent vascular involvement: Cholangiocarcinoma at the hilum of the liver sometimes invades the growth to the extrahepatic bile duct, and can invade the hepatic artery and main portal vein behind it. If the tumor is large and the metastasis is extensive, resection surgery should be abandoned; If the lesion does not belong to a particularly advanced stage, only invades part of the hepatic artery and (or) portal vein, and the vascular exposure is relatively easy, tumor resection including partial vascular resection can be performed.
If cholangiocarcinoma invades the固有artery of the liver, a segment of the artery can be resected, and the common hepatic artery and the固有artery of the liver can be fully mobilized, which is often capable of end-to-end anastomosis. If it invades the left hepatic artery or the right hepatic artery, and liver lobectomy is required, it is natural to resect the blood supply artery of the affected liver lobe; If liver lobectomy is not performed, generally speaking, the left hepatic artery or the right hepatic artery is severed, as long as the portal vein patency is maintained, it will not cause liver necrosis, unless the patient has severe jaundice and liver function is compensated, such as cholangiocarcinoma invades the main trunk of the portal vein, when the range is relatively small, it can first be fully mobilized at the non-cancer invaded area, and the portal vein at the upper and lower ends of the粘连part with the tumor can be controlled by a atraumatic vascular clamp, and the tumor along with a small part of the portal vein wall can be resected, and the portal vein can be repaired with 5-0 atraumatic suture line. If the portal vein is invaded and a segment needs to be resected, it is best to adopt end-to-end anastomosis to achieve a higher success rate; If the length of the resected portal vein exceeds 2cm, it should use the iliac external vein or GoreTex artificial vascular graft to bridge吻合, this method because the pressure difference between the two sides of the portal vein is small, the incidence of occlusion is higher, should be avoided as much as possible.
⑧ Liver transplantation for hilar bile duct cancer: Liver transplantation for hilar bile duct cancer must be strictly selected for cases, because the recurrence rate of cancer after liver transplantation is relatively high, reaching 20% to 80%.
Factors affecting the recurrence of bile duct cancer after liver transplantation include:
A, Perihepatic lymph node metastasis status: The recipients with cancer infiltration around the liver survive only 7.25 months, while those without infiltration survive for 35 months;
B, Tumor staging: UICC staging III, IV, there is no case surviving for 3 years after transplantation, while about half of the patients with stage I and II survive for more than 5 years after transplantation;
C, Vascular invasion situation: The average survival time of liver transplantation for patients with vascular invasion and without vascular invasion is 18 months and 41 months, respectively. Therefore, liver transplantation is only considered for bile duct cancer under the following conditions:
a, Laparotomy is definitely UICC stage II;
b, Intraoperative, due to tumor infiltration, it is not possible to complete R0 resection and can only perform R1 or R2 resection;
c, For patients with focal recurrence within the liver after liver transplantation, radiotherapy must be adopted to achieve certain efficacy.
⑨ Internal drainage surgery for hilar bile duct cancer: For inoperable bile duct cancer, internal drainage surgery is the preferred option, which can improve the patient's overall condition and quality of life for a certain period of time. It is suitable for significant intrapulmonary bile duct dilatation, without acute infection, and the liver lobe to be drained has a function. The surgical method is different according to the type of classification.
A, Left intrahepatic bile duct jejunal anastomosis: Suitable for Bismuth type III and a few type IV lesions, the classic operation is Longmire surgery, but it requires the resection of the left lateral lobe of the liver, which results in a large surgical trauma and is not suitable for obstruction at the bifurcation of the bile duct. The commonly used method at present is the third segment of the round ligament route of the bile duct jejunal anastomosis. This segment of the bile duct is located on the left side of the round ligament and falciform ligament, in front of the left branch of the portal vein, on the anterior edge of the liver, and after incising the peritoneum on the visceral surface, the liver tissue should first encounter this segment of the bile duct. The operation is easy, and the bile duct can be incised along the longitudinal axis by 0.5 to 1.0 cm, and then anastomosed with the jejunum in a Roux-en-Y fashion. This method has the advantages of minimal trauma, simplicity, and safety. When the left lobe of the liver has a certain compensatory function, the drainage effect is better. The disadvantage is that it cannot drain the entire liver. To achieve the purpose of simultaneously draining the right lobe of the liver, an U-shaped tube can be added for drainage. A probe is inserted into the incision of the third segment of the bile duct, passing through the narrow segment of the confluence into the proximal obstruction of the right bile duct, and then a silicone U-tube is introduced. The bile of the right bile duct enters the left bile duct through the lateral holes of the U-tube and then enters the intestine through the anastomosis.
B. Right intrahepatic bile duct-jejunum anastomosis: The course of the right intrahepatic bile duct is not as constant as that of the left, making it relatively difficult to locate. The most common method is to incise the lower segment of the right anterior lobe bile duct from the gallbladder bed, anastomose it with the gallbladder- duodenum, or perform a Roux-en-Y anastomosis with the jejunum. According to the anatomy of the hilum, the bile duct in this segment is only 1-2 cm deep at the gallbladder bed. When the intrahepatic bile duct dilates, it is easy to incise and find it at this location, and then expand the incision to provide anastomosis. During the operation, the gallbladder is first freed, attention is paid to preserve blood supply, and then the gallbladder can also be used as an interspersed object. After anastomosing the gallbladder with the right intrahepatic bile duct, it is then anastomosed with the duodenum or jejunum to perform a Roux-en-Y anastomosis, making the operation easier.
C. Bilateral bile duct-jejunum anastomosis: For type IIIa or IIIb and type VI cholangiocarcinoma, hemiliver drainage is insufficient. Theoretically, hemiliver drainage can maintain necessary liver function, but in reality, it is not enough to relieve jaundice, improve nutrition, and improve the quality of life. Therefore, except for type I and II cholangiocarcinoma, bilateral bile duct-jejunum anastomosis should be performed for other types if possible, using the same exposure and anastomosis methods as mentioned above.
2. Surgical treatment of middle and lower segment cholangiocarcinoma: For cholangiocarcinoma located in the middle segment, if the tumor is relatively localized, partial resection of the bile duct at the site of the tumor, cholecystoduodenal ligament lymph node dissection, and Roux-en-Y anastomosis between the common hepatic duct and jejunum can be performed; for lower segment cholangiocarcinoma, generally a pancreaticoduodenectomy (Whipple operation) is required. The key to the effectiveness of the operation is whether the cholecystoduodenal ligament can be cleared to 'skeletonization'. However, some scholars believe that middle and lower segment cholangiocarcinoma have a high degree of malignancy, develop rapidly, and are prone to metastasis to the posterior pancreas and pericardial aortic lymph nodes. Radical resection should include extensive resection of the gallbladder, common bile duct, pancreatic head, and duodenum, along with thorough dissection of the cholecystoduodenal ligament. This issue should be handled according to the 'individualization' principle, making corresponding treatments for different patients and not generalized. Preoperative preparation and incisions, explorations, etc., are the same as those for hilar cholangiocarcinoma.
(1) Excision of middle segment cholangiocarcinoma: For early, localized, and well-differentiated tumors, especially papillary adenocarcinoma growing into the lumen, cholecystoduodenal ligament dissection and excision of the soft tissues such as lymph nodes and nerves can be performed. See the surgical methods for hilar cholangiocarcinoma for reference, but the excision range of the upper bile duct should reach the common hepatic duct. It is best to excise 2.0 cm away from the upper margin of the tumor. Reconstruction of the bile duct should be done with a Roux-en-Y anastomosis between the common hepatic duct and jejunum. Alternatively, a common hepatic duct-interspersed jejunum-duodenum anastomosis can be used, but this is more complicated and the efficacy is similar to the former, so it is generally not adopted.
(2) Resection of lower bile duct cancer:
①Whippie surgery and its modified methods: In 1935, Whippie first applied the pancreatoduodenectomy to treat periampullary tumors, achieving good results. For patients with bile duct cancer, this operation requires good general condition and age.
The main methods of gastrointestinal reconstruction after pancreatoduodenectomy include: A, Whippie method: The sequence is biliary-enteric, pancreatic-enteric, and gastrointestinal anastomosis. The pancreatic-enteric anastomosis can be performed by end-to-side method, and the pancreatic duct is anastomosed with the mucosa of the jejunum. However, it is more difficult when the pancreatic duct is not dilated, and it is easy to occur pancreatic fistula. B, Child method: The sequence of anastomosis is pancreatic-enteric, biliary-enteric, and gastrointestinal anastomosis. The incidence of pancreatic fistula in the Child method is significantly lower than that in the Whippie method. Once pancreatic fistula occurs in this method, only pancreatic juice is excreted. As long as the drainage is unobstructed, there is still a chance for healing. Both the Whippie and Child methods place the gastrointestinal anastomosis below the pancreatic-enteric and biliary-enteric anastomosis. Bile and pancreatic juice are neutralized through the gastrointestinal anastomosis, which helps to reduce the occurrence of anastomotic ulcers. C, Cattell method: The sequence of anastomosis is gastrointestinal, pancreatic-enteric, and biliary-enteric.
②Preservation of the pylorus pancreatoduodenectomy (PPPD): Retain the whole stomach, pylorus, and duodenal bulb, and transect the duodenum 2-4 cm beyond the pylorus, anastomosing the distal end with the beginning of the jejunum. The rest of the scope is the same as the Whippie operation. It was first advocated by Travetso and Longmire in 1978. Since the 1980s, due to the emphasis on the quality of life, its application has gradually increased. The advantages of this operation are: it simplifies the surgical operation, shortens the operation time, retains the digestive and storage function of the stomach, promotes digestion, prevents dumping syndrome, and is conducive to improving nutrition. It avoids complications related to subtotal gastrectomy. The premise of performing this operation is that the malignancy of the tumor is not high, and there is no metastasis of the lymph nodes above and below the pylorus. Whether this operation affects the radicality of treatment for bile duct cancer in the lower segment is generally not controversial, but attention should be paid to the prevention and treatment of some complications, mainly delayed gastric emptying after surgery. Delayed gastric emptying refers to the inability to take liquid food by mouth 10 days after surgery, with an incidence rate of 27% to 30%. The possible reasons may be the interruption of the right gastric artery, affecting the blood supply to the pylorus and duodenum, the destruction of the integrity of the vagus nerve's claw, the removal of the peristaltic pacemaker of the duodenum, and the suppression of the gastric motility pacemaker. Most delayed gastric emptying can be cured by non-surgical therapies such as gastrointestinal decompression and nutritional metabolism support, but sometimes long-term non-healing may require gastrostomy.
③ Local resection of the duodenal papilla.
A. Indications: Distal bile duct cancer is limited to the ampulla of Vater or the duodenal papilla; patients with an older age or with systemic diseases are not suitable for pancreaticoduodenectomy. It is necessary to prove that the bile duct tumor is limited to the distal end through imaging examination and duodenoscopy before surgery.
B. Surgical Method: Further exploration and verification should be conducted to prove the feasibility of this surgical procedure. Incise the lateral peritoneum of the duodenum, fully mobilize the duodenum, and with the thumb and index finger of the left hand, palpate the enlargement of the papilla on the outside of the intestinal wall. Make a longitudinal incision on the duodenal wall opposite the papilla (anterior and lateral wall of the duodenum), where an enlarged duodenal papilla protruding into the intestinal lumen can be seen. Make a longitudinal incision in the common bile duct and insert a bile duct probe through the bile duct incision, attempting to pull the probe out from the papillary orifice as much as possible. Combine upper and lower exploration to clarify the size and mobility of the tumor. After confirming the surgery, suture two牵引 lines on both sides of the bile duct above the papilla, and make a transverse incision on the posterior wall of the duodenum 0.5cm above the牵引 line using a high-frequency electrosurgical knife, until the dilated bile duct is incised, and bile can be seen flowing out. Gently pull the papilla downward and suture the posterior wall of the duodenum and the distal common bile duct with absorbable suture. Continue to expand the incision around the duodenal papilla to the left, suture the duodenum and bile duct as you cut, until the opening of the pancreatic duct is visible. After seeing the opening of the pancreatic duct, suture its upper wall with the common bile duct to form a common orifice, and suture the anterior wall with the duodenal wall. Use the same method to incise and suture the posterior wall of the duodenum below and on the right side, as you cut and suture, until the tumor is completely resected. At the same time, the anastomosis of the entire posterior and medial wall of the duodenum with the distal common bile duct and pancreatic duct is also completed. Insert a silicone tube with a diameter that matches the pancreatic duct, suture and fix it in the pancreatic duct, and place the other end in the intestinal lumen, about 15cm long. Place a T-tube for routine drainage in the common bile duct.
④ Lower segment bile duct cancer biliary diversion surgery: Compared to hilar bile duct cancer, it is relatively easier. Generally, the bile duct above the obstruction site is chosen to perform a Roux-en-Y anastomosis with the jejunum. When there is an obstruction in the lower segment bile duct, performing a cholecystojejunostomy is simpler. However, the confluence of the gallbladder and bile duct is prone to be invaded by cholangiocarcinoma and blocked. Even if it is not blocked, clinical findings show that its drainage effect is poor, so it should be avoided as much as possible. The site of anastomosis should be as high as possible in the common bile duct, and the bile duct should be cut and the distal end ligated, and the proximal end anastomosed with the jejunum. It is not advisable to choose a bile duct duodenal anastomosis, as the excessive inversion of the duodenum can increase the tension at the anastomosis site, and with the presence of bile duct tumors, they can quickly invade the anastomosis site. As the lower segment bile duct cancer grows, it may cause duodenal obstruction. Depending on the situation, a gastrojejunostomy can be performed to bypass the duodenum that may be obstructed by the tumor.
⑤ Caution should be exercised when performing PTCD: There have been two different views on whether to perform PTCD before surgery for patients with cholangiocarcinoma. Japanese scholars believe that performing biliary tract drainage and decompression before surgery to reduce the total bilirubin level can extend the postoperative survival period, but the prospective clinical research results from the UK, the US, and South Africa do not support the view that preoperative biliary decompression can improve the prognosis of patients with extrahepatic cholangiocarcinoma. Huang Zhiqiang from China also advocates against performing PTCD before surgery for extrahepatic cholangiocarcinoma, and the reason is:
A. PTCD is prone to cause biliary tract infection, and severe suppurative cholangitis may result in the loss of the opportunity for a definitive surgical procedure.
B. The intraperitoneal bile ducts are obstructed in a segmented manner, and unilateral drainage cannot achieve the expected effect of draining all the intraperitoneal bile ducts.
C. Although the serum bilirubin level decreases after drainage, the liver cell function has not been restored.
D. PTCD itself can be associated with complications such as significant bile loss, bile leakage, peritonitis, intraperitoneal hemorrhage, catheter pain, and inconvenience.
Therefore, it is believed that caution should be exercised when performing PTCD in patients with extrahepatic cholangiocarcinoma.
3. Other treatments
(1) Radiotherapy for cholangiocarcinoma: In the past, it was believed that cholangiocarcinoma was insensitive to radiotherapy, and radiotherapy was even abandoned in clinical practice. In the past 20 years, extensive research has been conducted on radiotherapy for cholangiocarcinoma. Some literature reports that radiotherapy can alleviate the symptoms of cholangiocarcinoma patients and may extend survival, achieving certain effects. Radiotherapy can be used as the main treatment method for cholangiocarcinoma, and can also be used as adjuvant treatment for surgery. The main methods include traditional external beam therapy, intraoperative irradiation therapy, internal irradiation therapy, and radioimmunotherapy. The purpose of radiotherapy is: A. To reduce the tumor size, which helps to re-open the bile duct and alleviate jaundice; B. To alleviate the tumor compression and reduce the degree of pain in patients; C. To slow down the growth rate of the tumor or to reduce the tumor size, maintain the patency of the bile duct through a stent, and extend the survival of patients through these effects.
①External beam radiotherapy for cholangiocarcinoma: There are various forms of external beam radiotherapy, usually using cobalt-60 or linear accelerators. According to CT examination positioning, 3 to 4 fields are irradiated at a dose of 2.0 Gy per day, with a total dose of 45 to 60 Gy. Due to the presence of important organs such as the liver, right kidney, spinal cord, duodenum, and stomach within the radiation field, custom boards are used to protect these organs during irradiation, in order to minimize radiation damage. If radiotherapy is performed after surgery, metallic markers should be placed during surgery to indicate the irradiation field, making the positioning more accurate. This can reduce the radiation field and minimize secondary damage. For patients with metallic stent placement in the bile duct, the effect of anterior and posterior through-irradiation is better, but since the ends of the stent are often blocked by growing tumors, the irradiation range should exceed the stent. There are reports that cobalt-60 external beam radiotherapy can produce significant effects in 50% of patients, including pain relief, jaundice reduction, or tumor shrinkage, and is particularly effective for patients with residual cancer cells at the residual bile duct after tumor resection, significantly extending survival. There are also reports of stereotactic radiotherapy for cholangiocarcinoma using X-ray irradiation, with CT scan positioning and the creation of a three-dimensional plan, indicating CTV (clinical tumor volume) and PTV (planned tumor volume). The entry direction and weight of each irradiation field are adjusted according to the isodose curve and dose-volume histogram. Generally, 5 to 6 fields are arranged, with 80% to 90% of the isodose lines enveloping the PTV and normalized. The tumor dose is 35 Gy, and it is irradiated 7 times in total over 14 days, or the tumor dose is 36 Gy, and it is irradiated 6 times in total over 12 days. Observations show that the tumor shrinks, and it has a good effect on alleviating symptoms such as jaundice. In 1997, Pederson et al. reported on the in vitro and animal experiments of the killing effect of molecular chemotherapy + radiotherapy sensitization on cholangiocarcinoma cells. This method utilizes methods of molecular biology to construct a toxin gene/prodrug complex, converting the prodrug 5-fluorouracil (5-FU) to 5-fluorocytosine inside the cell, thereby enhancing the intracellular toxic effect of 5-FU and achieving the purpose of killing a large number of cholangiocarcinoma cells. At the same time, it utilizes the radiosensitizing effect of 5-FU, followed by cobalt-60 radiotherapy. It is reported that the effect is significant. This method of toxin gene/prodrug chemotherapy + radiotherapy may become a new strategy for the comprehensive treatment of cholangiocarcinoma.
Acute side effects are usually not very severe, such as nausea, duodenitis, etc., but sometimes cholangitis and bile duct hemorrhage can occur, which require timely treatment. In the later stage, there may be duodenal injury and bile duct stenosis.
② Advantages of intracavitary radiotherapy for bile duct cancer: It can achieve high-dose irradiation of the lesion locally while causing minimal damage to surrounding normal tissue.
Intracavitary radiotherapy is usually performed through PTC or ERCP, or through a T tube or U tube placed during surgery, with the radioactive source 192Ir placed near the bile duct tumor for irradiation. The dose is generally 7-8Gy per session, with a 5-7 day interval between sessions, for a total of 4 sessions, with a total dose of 28-36Gy. If postoperative pipeline access is used for radiotherapy, a channel can be reserved during surgery, and the bile duct stenosis can be gradually expanded through the common bile duct, reaching an inner diameter of 6-9mm. A silicone single tube is inserted as a support and for drainage, with the drainage tube directly exiting from the incision of the common bile duct exploration. This creates an angle greater than 120° between the common bile duct and the support drainage tube, facilitating the entry of the radioactive source into the bile duct to the tumor site. Radiotherapy can be performed 2 weeks after the condition stabilizes postoperatively, and according to reports, the effect is good, even in some cases, the tumor disappears after 2-3 sessions of irradiation followed by fiberoptic cholangioscopy.
Disadvantages: A, Most patients cannot receive sufficient doses of radiation to kill tumor cells with simple internal radiation. B, High doses, such as 20Gy in 2 days, can cause necrosis of bile duct epithelial cells and lead to bile duct stenosis and sclerosis. C, Tumor tissue located at a certain distance from the lumen will be ineffective.
③ Combined radiotherapy for bile duct cancer: The combined application of external and intracavitary radiotherapy takes advantage of the complementary strengths of both to improve efficacy and reduce adverse reactions. For patients who have not undergone surgery, intracavitary radiotherapy can be performed through PTC or ERCP tubes. For patients who have received surgery and have reserved radiotherapy channels, combined radiotherapy is particularly suitable and should achieve better efficacy than the application of a single therapy.
④ Radiotherapy during surgery for bile duct cancer:
Advantages: A, It can achieve direct and effective radiotherapy for the tumor, with a large single dose of radiation. B, The non-irradiated areas can be covered, protecting the surrounding important organs. C, The use of electron beams allows for a larger dose of radiation to superficial areas, with faster radioactive decay. D, The depth of radiation can be arbitrarily adjusted, and an energy of 6-22MeV is usually sufficient to treat a tumor thickness of 6cm.
Limitations: A, The equipment conditions require a high standard, and it is very cumbersome and risky for patients to undergo abdominal surgery in the operating room and then receive radiotherapy in the radiotherapy department, followed by returning to the operating room for further surgery. B, Some tissues cannot tolerate a single high dose of radiation. The hepatic artery and portal vein can tolerate a single dose of 45Gy of radiotherapy, while the bile duct can develop fibrosis after a single dose of 15Gy of radiotherapy. Radiotherapy doses greater than 30-40Gy can lead to secondary sclerosis of the bile duct. C, Even with a single high-dose irradiation, it may still be insufficient to control the tumor.
Improvements: A, combining relatively low-dose intraoperative radiotherapy with external beam radiotherapy, B, combining intraoperative radiotherapy with the use of radiotherapy sensitizers, which can make hypoxic cells more sensitive to radiotherapy.
(2)Chemotherapy for cholangiocarcinoma: Cholangiocarcinoma is less sensitive to chemotherapy than other gastrointestinal tumors such as colon cancer, and the reason is unclear. It may be related to the drug resistance of cholangiocarcinoma, low drug concentration in the tumor, and other factors. Therefore, there is still no effective and reliable chemotherapy regimen for cholangiocarcinoma at present. There are reports that the sensitivity of 10 cases of hilar cholangiocarcinoma cells to chemotherapy drugs was detected by the MTT method, and the sensitivity rates of 8 drugs were as follows: epirubicin (epi-adriamycin) 60%, doxorubicin (adriamycin) 40%, cisplatin 30%, carboplatin 30%, mitomycin 20%, methotrexate 10%, fluorouracil (5-Fu) 0%, cyclophosphamide 0%. However, in fact, the clinical application effect of most cases did not reach the above efficiency. In 1997, Lersch reported that the response rate of single-agent chemotherapy was only 12%, while the response rate of combined chemotherapy reached 23%.
①Treatment chemotherapy for advanced cholangiocarcinoma: The commonly used chemotherapy drugs are similar to those for other gastrointestinal cancers, mainly fluorouracil (5-FU), doxorubicin (adriamycin), mitomycin (MMC), and nitrosourea, etc., which can be administered systemically or via arterial catheterization. Since the blood supply of the bile duct comes from the hepatic artery, arterial chemotherapy may have better efficacy than the former. Some studies have indeed shown that chemotherapy may alleviate the symptoms caused by cholangiocarcinoma, improve the quality of life of patients, and may also prolong survival. One report involved 49 patients, where chemotherapy with fluorouracil (5-FU) as the main drug was used in the treatment group, and another group of 41 patients only received general care. The treatment group had 36% of patients who extended their high-quality life for 4 months, with a median survival period of 6 months in the former, while only 2.5 months in the latter.
②Auxiliary surgical treatment: Neoadjuvant chemoradiotherapy, that is, chemotherapy and radiotherapy are first applied to solid tumors, followed by surgery, and then supplemented with chemotherapy and radiotherapy after surgery. The theoretical basis is effective combined chemotherapy before surgery or before radiotherapy to kill a large number of sensitive tumor cells, reduce the vitality of tumor cells, and then use surgery to resect or radiotherapy to destroy the remaining cells including those that are not sensitive to chemotherapy, with the aim of curing the tumor. Some scholars have applied this regimen to the treatment of hilar cholangiocarcinoma, usually intravenously infused with fluorouracil (5-FU) [300mg/(m2·d)] for 5 days before surgery, followed by external beam radiotherapy to the tumor site (1.8Gy/d, total dose not exceeding 50Gy). The result was an increase in the resection rate and a decrease in the microscopic residual rate of cancer cells at the bile duct margin, thereby reducing local recurrence. However, whether it can improve survival rate is still inconclusive.
③ Combined with radiotherapy: The application of some recognized radiosensitizers such as 5-FU can improve the efficacy of radiotherapy. The in vitro and animal experimental studies on the antitumor effects of molecular chemotherapy and radiosensitization have achieved satisfactory results, providing a new approach for the comprehensive treatment of cholangiocarcinoma. Minsky used 5-FU and mitomycin C in combination with radiotherapy: the radiation dose to the tumor bed and lymph nodes was 50Gy, and most patients also received 15Gy of intracavitary radiotherapy, which was well tolerated by the patients. The 3-year survival rate reached 50%. Additionally, the use of external radiotherapy and 5-FU chemotherapy after surgery can reduce the dose of radiotherapy.
II. Prognosis
The prognosis of cholangiocarcinoma is very poor, and it is related to the clinical type, pathological characteristics, and treatment methods. Cholangiocarcinoma does not undergo any surgery or drainage, and most patients die within 3 months after diagnosis. The 1-year and 3-year survival rates of patients with more thorough tumor resection are 90% and 40% respectively, while those undergoing palliative surgery are only 55% and 10%. The survival time of patients with simple drainage is rarely more than 1 year. In literature reports, the survival periods of upper, middle, and lower segment cholangiocarcinoma are (8.75±6.31), (10.31±8.01), and (14.48±12.95) months respectively, with the shortest survival period in the upper segment and the longest in the lower segment. Cholangiocarcinoma with infiltrative, poorly differentiated, lymph node metastasis, and liver metastasis has a significantly shorter survival period, indicating poor prognosis. Cholangiocarcinoma with papillary, moderately to poorly differentiated, without lymph node metastasis, and liver metastasis has a relatively better prognosis. The prognosis comparison of different treatment methods shows that surgical resection is the best, significantly better than simple biliary decompression surgery. Therefore, for patients with cholangiocarcinoma who have conditions, it is recommended to perform radical resection as early as possible. Although surgical resection can achieve short-term efficacy, the long-term effect is still not satisfactory, with a high local recurrence rate. Therefore, new breakthroughs are needed to break away from the current situation and make progress.
