Gallbladder cancer is a common tumor of the bile duct system, accounting for about 2/3 of biliary tract tumors. Its incidence rate ranks 6th in the gastrointestinal tract after gastric cancer, esophageal cancer, colorectal cancer, liver cancer and pancreatic cancer and is on the rise, accounting for 0.76%~1.2% of all cancers in China and 0.4%~3.8% of biliary tract diseases. The incidence rate of gallbladder cancer is related to gender, and the ratio of male to female incidence is about 1:2~4. The incidence rate of gallbladder cancer is mostly in elderly patients, and the incidence rates of patients over 50 and under 50 are 5%~9% and 0.3%~0.7% respectively. The incidence rates are 5-9% and 0.3%~0.7% for patients over and under 50 years old, respectively. Gallbladder cancer has an insidious onset and no specific clinical manifestations in the early stage, and it is often combined with gallbladder disease: 49.7% of gallbladder cancer patients in China are combined with gallbladder stones, and up to 95% of gallbladder cancer patients in the United States are combined with gallbladder stones. Due to the interference of gallbladder disease history for many years, the diagnosis is easily delayed, and most gallbladder cancers are already in the middle and late stages when diagnosed, and the early diagnosis rate is only 19.1%. Gallbladder cancer is highly malignant, with a low radical resection rate and a very poor prognosis, and the 5-year survival rate after surgery is less than 5% in most reports. Surgery is currently the preferred treatment for gallbladder cancer, and the application value of radiotherapy and chemotherapy needs further study. How to improve the early diagnosis rate, surgical resection rate and long-term survival rate of gallbladder cancer is still a pressing problem in hepatobiliary surgery today.
I. Relationship between gallbladder stones and gallbladder cancer
Gallbladder stones are closely related to the occurrence of gallbladder cancer. The risk of gallbladder cancer in patients with gallbladder stones is 6-15 times higher than that in patients without gallbladder stones, and gallbladder cancer can occur in 6-10% of patients with gallbladder stones over 50 years old, and the earlier the age of onset, the higher the risk of gallbladder cancer. The process of gallbladder cancer induced by gallbladder stones: cholelithiasis/cholangitis → mucosal epithelial hyperplasia of gallbladder → partial appearance of atypical hyperplasia → in situ cancer in mild cases, and infiltrative cancer in severe atypical hyperplasia.
High risk factors of gallbladder cancer
1. Female gallbladder stone patients over 50 years old
2. Gallstones with disease duration >5~10 years or stone diameter >2~3 cm
3, gallbladder neck stones or Mirizzi syndrome.
4, B-ultrasound suggesting uneven, restricted thickening or atrophy of the gallbladder wall.
5, adenomyosis of the gallbladder, gallbladder polyp-like lesions, especially in the neck and body, diameter > 1 cm.
6, porcelain-like gallbladder.
7. those who have undergone cholecystostomy.
8, abnormal pancreaticobiliary duct connection
Clinical manifestations
The most common clinical symptom of gallbladder cancer is pain in the right upper abdomen in 84% of gallbladder cancers. Since gallbladder cancer mostly coexists with gallbladder stones and cholecystitis, the nature of pain is very similar to that of stone cholecystitis, which starts with discomfort in the right upper abdomen, followed by persistent hidden pain or dull pain, and the pain may radiate to the right shoulder. Early stage gallbladder cancer has no specific clinical manifestations, so it is easy to mistake gallbladder stones and cholecystitis for jaundice, and when jaundice appears, it is already in the middle and late stage. At present, the early diagnosis of gallbladder cancer is still difficult, and most cases are already in the middle and late stages when diagnosed, so the prognosis is very poor. In order to improve the prognosis, it is necessary to enhance the vigilance of gallbladder cancer, to make good screening and monitoring of patients with high-risk factors, and to achieve early diagnosis and treatment in order to improve the long-term survival rate.
IV. Examination means
Ultrasound examination and CT or MRI examination if necessary. At present, ultrasound is still the first choice for gallbladder cancer examination at home and abroad, and the correct diagnosis rate can reach 70%~88%, but it is still difficult to detect early stage gallbladder cancer (23.0%). Endoscopic ultrasound (EUS) is a technique developed in recent years, which can help improve the early diagnosis of gallbladder cancer because it avoids the interference of intestine and can determine the extent of tumor infiltration in all layers of gallbladder wall, while CT examination has important reference value in determining the extent of gallbladder cancer invasion and expansion and the selection of surgical methods. MRI has important reference value in the selection of surgical treatment plan for gallbladder cancer with jaundice.
V. Pathological types and biological characteristics of gallbladder cancer
80-98% of gallbladder cancers are adenocarcinoma, while a few are adenosquamous, squamous, mucinous and undifferentiated cancers. The most common metastasis is lymphatic metastasis, and the lymph node metastasis rate of progressive gallbladder cancer can be as high as 62.5%~73.0%; gallbladder cancer easily invades the liver, duodenum, bile duct, gastric sinus, colon and other surrounding organs.
Surgical methods
Surgical resection is the only treatment method for gallbladder cancer patients to achieve long-term survival. The treatment methods of gallbladder cancer include cholecystectomy, radical surgery of gallbladder cancer, extended radical surgery of gallbladder cancer, palliative resection of gallbladder cancer, internal and external biliary drainage, and so on. Different surgical methods should be used according to the different stages, tumor invasion sites and lymphatic metastasis.
(1) Simple cholecystectomy: For patients with Nevin stage I and T1aN0M0 gallbladder cancer, cholecystectomy is sufficient to achieve radical treatment without lymph node dissection.
(2) Standard radical cholecystectomy: For patients with Nevin stage II, III, IV, part of V and T2N0M0, the operation requires complete resection of the gallbladder, appropriate resection of liver tissue in the gallbladder bed area, and whole resection of lymph nodes in the hepatoduodenal ligament and lymph nodes in the parahepatic artery, pancreatic head and posterior duodenum.
(3) Extended radical surgery for gallbladder cancer: additional extensive hepatectomy, pancreaticoduodenectomy, combined sinus or colon resection, and lymph node dissection of the para-aortic abdomen, etc. Extended radical surgery may benefit some patients who cannot achieve R0 resection by conventional methods.
(4) Palliative surgery: simple cholecystectomy for patients who cannot be radically resected can also delay the invasion and obstruction of tumor to surrounding organs.
VII. Principles of radical surgery for gallbladder cancer
In view of the biological characteristics of gallbladder cancer with direct infiltration and lymphatic metastasis, combined partial resection of the liver and the whole tumor as well as regional lymph node dissection should be the standard for radical resection of gallbladder cancer. A reasonable surgical plan should be adopted according to the different TNM stages of gallbladder cancer and the extent of tumor invasion.
(1) Nevin I stage, stage 0 (Tis) of TNM stage and T1aN0M0 of stage I (the tumor only invades the lamina propria) can be radically resected by simple cholecystectomy. This type of patient is most commonly seen with unexpected gallbladder cancer and may not require reoperation. For stage I T1bN0M0 gallbladder cancer (tumor invades the muscular layer), because there may be early lymphatic metastasis, if it is an accidental gallbladder cancer, it is recommended to perform radical surgery for gallbladder cancer in order to improve the patient’s prognosis.
(2) For TNM stage II, IIIA and IIIB gallbladder cancer, the main surgical method is radical gallbladder cancer surgery. However, if the gallbladder cancer invades other organs outside the liver and requires combined organ resection, the surgery should be extended radical surgery for gallbladder cancer. stage IIIB (T1-3N1M0) gallbladder cancer combined with hilar lymph node metastasis, the surgery should emphasize the clearance of regional lymph nodes.
(3) Stage IV gallbladder cancer with TNM staging: divided into IVA (T4N0-1M0) and IVB (T1-4N2M0, T1-4N1-2M1). Stage IV gallbladder cancer has multiple organ invasion, distant lymph node metastasis or distant metastasis of other organs, and the prognosis is extremely poor, and the principles of surgery are currently more controversial. However, in view of the difficulty of early diagnosis of gallbladder cancer and the fact that most patients have already invaded other organs such as liver, extrahepatic bile ducts, gastric sinus or colon when they are diagnosed, extended radical surgery for gallbladder cancer is more frequently used in clinical practice and has become one of the important means of treatment for advanced gallbladder cancer. If the combined multi-organ resection can achieve negative margins, and the complications and surgical mortality are within the acceptable range, the combined hepatobiliary-pancreatic resection (HPD) in extended radical resection of gallbladder cancer can even be considered in stage IVA.