| disease | Gallbladder Cancer (Surgery) |
Primary gallbladder cancer is relatively rare in clinical practice and did not receive much attention for a long time. According to domestic textbook reports, it accounts for only about 1% of all cancers. With the widespread use of imaging examinations such as B-ultrasound and CT, gallbladder cancer has gradually been recognized, and its detection rate has increased. However, there are significant regional differences in the incidence of gallbladder cancer. In India, Gupta reported that the incidence of gallbladder cancer accounts for 2.9% of all cancers and 31.8% of gastrointestinal malignancies. In the United States, it ranks behind rectal, colon, pancreatic, and gastric cancers in gastrointestinal tumors, accounting for 3% of gastrointestinal tumors. The incidence of gallbladder cancer is higher in women than in men, with 90% of cases occurring in individuals over 50 years old.
bubble_chart Etiology
The cause of gallbladder cancer remains unclear. Clinical observations indicate that gallbladder cancer often coexists with benign gallbladder diseases, most commonly gallstones. Many believe that chronic irritation from gallstones is a significant causative factor. Moosa noted that among patients with "silent stones," 3.3% to 50% developed gallbladder cancer after 5 to 20 years. Domestic data reports that 20% to 82.6% of gallbladder cancer cases are associated with gallstones, while international reports indicate rates as high as 54.3% to 100%. The occurrence of cancer is closely related to the size of the stones. The incidence rate is 1.0 for stones smaller than 10 mm in diameter, 2.4 for stones 20–22 mm in diameter, and as high as 10 for stones larger than 30 mm in diameter. Some also suggest that the development of gallbladder cancer may be linked to malformations at the junction of the common bile duct and the main pancreatic duct in patients. Such malformations allow pancreatic juice to enter the bile duct, increasing the concentration of pancreatic juice in the gallbladder and leading to chronic inflammation, mucosal changes, and eventual cancerous transformation.
bubble_chart Pathological ChangesGallbladder cancer most commonly occurs in the fundus, followed by the neck, and less frequently in the body. Histologically, adenocarcinoma accounts for 80%, undifferentiated carcinoma for 6%, squamous cell carcinoma for 3%, and mixed carcinoma for 1%. Gallbladder cancer can directly infiltrate surrounding organs and may metastasize via lymphatic pathways, blood circulation, nerves, bile ducts, or through intraperitoneal seeding. Advanced-stage patients may develop distant metastases, but this generally occurs later and less frequently.
bubble_chart Clinical Manifestations
The clinical symptoms of gallbladder cancer include pain and discomfort in the mid-upper and right upper abdomen, indigestion, belching, loss of appetite, jaundice, and weight loss. Since the vast majority of patients also have gallstones, the clinical pain is similar to that of calculous cholecystitis. In the late stage (third stage), the pain becomes a persistent dull ache. Jaundice is often a symptom of the advanced stage and is accompanied by cachexia. When the cystic duct is blocked or the cancer metastasizes to the liver or adjacent organs, a firm mass may sometimes be palpated in the upper abdomen. If the cancer invades the duodenum, symptoms of pyloric obstruction may occur.
Gallbladder cancer lacks specific clinical manifestations in patients. Most cases are misdiagnosed as cholecystitis or cholelithiasis. Patients with symptoms such as right upper abdominal pain, right upper abdominal mass, or anemia often present at an advanced stage of the disease. In recent years, improvements in diagnostic capabilities have primarily relied on advancements in modern imaging techniques and a deeper understanding of the disease.
2. CT scan: The sensitivity of CT scans for gallbladder cancer is 50%, and it is less effective than US or EUS for diagnosing early-stage gallbladder cancer. CT imaging findings can be categorized into three types: ① Thickened wall type: localized or diffuse irregular thickening of the gallbladder wall. ② Nodular type: papillary nodules protruding from the gallbladder wall into the lumen, with the gallbladder cavity still present. ③ Solid type: a solid mass formed by extensive tumor infiltration of the gallbladder wall combined with filling of the cavity by cancerous tissue. CT can often detect tumor invasion of the liver or metastases to lymph nodes in the hepatic hilum or pancreatic head.
4. ERCP: Some reports indicate that ERCP can achieve a diagnostic rate of 70–90% for gallbladder cancer when the gallbladder is visualized. However, more than half of ERCP examinations fail to visualize the gallbladder. Imaging findings can be divided into three scenarios: (1) Good visualization of the gallbladder and bile ducts: mostly seen in early-stage cases, with typical cases showing filling defects or broad-based protrusive lesions connected to the gallbladder wall. Infiltration of the gallbladder wall may manifest as rigidity or deformation. (2) Non-visualization of the gallbladder: mostly seen in intermediate or advanced-stage cases. (3) Non-visualization of the gallbladder with narrowing of the hepatic or extrahepatic bile ducts: filling defects and dilation of the bile ducts above the obstruction are signs of advanced-stage disease.
5. Cytological examination: Cytological methods include direct biopsy or aspiration of bile to detect cancer cells. Direct biopsy methods include ultrasound-guided gallbladder lesion puncture, PTCCS (percutaneous transhepatic cholecystoscopy), and laparoscopy. Methods for bile collection are more varied, such as bile aspiration during ERCP, ultrasound-guided gallbladder puncture, PTCD, and cholangioscopy. Although the reported positive rate of cytological examination is not high, when combined with imaging methods, it can still diagnose more than half of gallbladder cancer cases.
6. Tumor markers: In immunohistochemical studies of tumor specimens, the CEA positivity rate for gallbladder cancer is 100%. Serum CEA levels in advanced gallbladder cancer patients can reach 9.6 ng/ml, but it has no value for early diagnosis. Tumor-associated glycoprotein antigens such as CA19-9, CA125, and CA15-3 can only serve as auxiliary tests for gallbladder cancer.
bubble_chart Treatment Measures
1. Surgical Treatment Principles for Gallbladder Cancer
(1) Principles of Radical Surgery for Occult Gallbladder Cancer: Occult gallbladder cancer refers to cases where the diagnosis is not made preoperatively or intraoperatively but is confirmed by pathological examination after cholecystectomy for "benign" disease. Since the diagnosis is made postoperatively, the issue is whether a second radical surgery is needed. If the pathological examination shows that the cancer has only invaded the mucosa or muscularis layers, complete cholecystectomy alone is sufficient for radical treatment, and a second radical surgery is unnecessary. Lymphatic metastasis of gallbladder cancer first involves the gallbladder triangle and lymph nodes along the common bile duct. Cancers located in the gallbladder neck, especially the cystic duct, are closer to the gallbladder triangle and thus more likely to metastasize to these lymph nodes early. The postoperative recurrence rate for gallbladder neck cancer is also significantly higher than for cancers in the body or fundus of the gallbladder. Therefore, for occult gallbladder cancer in the neck or cystic duct, regardless of the depth of invasion, a second surgery to clear lymph nodes around the hepatoduodenal ligament is warranted. Occult gallbladder cancer with invasion beyond the muscularis layer, positive margins, or positive biopsy of the gallbladder triangle lymph nodes should also undergo a second radical surgery.
(2) Radical Surgery for Gallbladder Cancer: Since most gallbladder cancer patients are not in the early stage at diagnosis, according to large case analyses, only about 23% of gallbladder cancers can be radically resected. The median survival for gallbladder cancer patients overall is 3 months, leading some surgeons to adopt a pessimistic attitude toward treatment. In recent years, the 5-year survival rate has significantly improved due to the implementation of radical surgeries. The scope of radical surgery mainly includes cholecystectomy, partial hepatectomy, and lymph node dissection. The liver is typically resected about 3 cm around the gallbladder bed. Lymph node dissection depends on drainage pathways and metastasis. Generally, dissection extends to the next station of metastatic lymph nodes. Early-stage gallbladder cancer may only require removal of gallbladder lymph nodes, but most resectable gallbladder cancers should involve dissection of hepatoduodenal ligament lymph nodes, and if necessary, the superior pancreaticoduodenal and posterior pancreatic head lymph nodes.
(3) Palliative Surgery for Advanced-Stage Gallbladder Cancer: For unresectable advanced-stage gallbladder cancer cases, the surgical principle is to alleviate pain and improve quality of life. A prominent issue in advanced-stage gallbladder cancer is obstructive jaundice caused by tumor invasion of the biliary system. Surgery should prioritize internal drainage. Methods include choledochojejunostomy, but due to deep local tumor infiltration, especially with hilar involvement, biliary-enteric internal drainage is often difficult. For such patients, bridging internal drainage can be performed. For patients in very poor general condition, external drainage via tube placement may be considered. For severe hilar invasion where the above procedures are unfeasible, the right liver can be incised using the scrape-and-suction method to locate dilated bile ducts for tube drainage.
2. Radiotherapy: Used only as an adjuvant therapy postoperatively or for unresectable cases. Todoroki reported a 3-year survival rate of 10.1% for gallbladder cancer with resection plus radiotherapy, compared to 0% without radiotherapy. The typical radiation dose is 40–50 Gy. Intraoperative radiotherapy involves delivering 20–30 Gy using electron beams from a cyclotron after tumor resection.
3. Chemotherapy: Gallbladder cancer is generally insensitive to chemotherapy drugs, making efficacy hard to observe. It is mostly used as adjuvant therapy postoperatively. Common drugs include ADM, 5-FU, and MMC. (6) Prognosis: The 5-year survival rate for gallbladder cancer is very low, around 2–5%; over 80% of patients die within 1 year. If the cancer is limited to the mucosa and submucosa, cholecystectomy yields a better prognosis, with some reports indicating a 5-year survival rate of 40–64% in this group. Thus, the key to a good prognosis lies in early diagnosis and timely treatment.
