How to treat primary gallbladder cancer

Primary gallbladder cancer is a highly invasive and metastatic malignant tumor. It is the most common malignant tumor of the biliary system. Its incidence ranks fifth to sixth among digestive tract malignancies, and has been on the rise in recent years. With the improvement of the diagnosis of gallbladder cancer and the improvement of surgical techniques such as liver resection combined with lymph node dissection, the efficacy of radical resection has once again attracted widespread attention and attention. At present, the staging and treatment of gallbladder cancer, the management of early and unexpected gallbladder cancer, and the standards for extended radical resection of gallbladder cancer are of great concern at home and abroad. This article reviews them as follows.

1. Gallbladder cancer staging and treatment

At present, there are three commonly used staging methods: TNM staging, Nevin staging and JSBS staging. Nevin staging and TNM staging are widely used at home and abroad. Most authors believe that TNM staging is a better staging method for comparing surgical effects and judging prognosis, and there are also relevant comparative statistical analyses at home and abroad to support it.

In the TNM staging, the T stage mainly describes the degree of tumor infiltration into the gallbladder wall and the invasion of adjacent organs. It is the main factor in selecting the appropriate surgical method and affecting prognosis. The gallbladder wall from the inside to the outside mainly consists of the mucosal layer, submucosal layer, muscular layer, connective tissue layer and serosa layer. The part of the gallbladder adjacent to the liver lacks the serosa layer, and the connective tissue layer is directly connected to the connective tissue of the liver. Gallbladder cancer confined to the gallbladder wall is T1 and T2 stages, and beyond the gallbladder wall is T3 and T4 stages. N staging requires histological examination of at least three regional lymph nodes, including the porta hepatis, celiac trunk, periduodenal, peripancreatic head and superior mesenteric lymph nodes. It is generally believed that lymph node metastasis beyond the hepatoduodenal ligament is considered to be distant metastasis. The most common distant metastasis of gallbladder cancer is abdominal and liver metastasis.

At present, most hepatobiliary surgeons at home and abroad believe that TNMI stage gallbladder cancer can be treated with simple cholecystectomy, II-III stage gallbladder cancer can be treated with radical resection, and some stage IV patients can be treated with extended radical resection of gallbladder cancer. However, there are still differences on whether extended radical resection of gallbladder cancer is necessary. Reports show that most scholars in China and Japan believe that radical resection can improve the prognosis of patients and increase survival, and there are many data reports showing good surgical results.

With the continuous standardization of gallbladder cancer treatment and the continuous improvement of statistical data, reports [6] show that the median survival and 1-, 3-, and 5-year survival rates (including cumulative and disease-free survival rates) of patients after radical resection of gallbladder cancer are significantly higher than those of patients who underwent simple cholecystectomy and palliative surgery, both overall and at each different stage level. Comprehensive data on the current surgical treatment of gallbladder cancer in China show that there are still some surgical plans that do not meet the treatment standards. For example, some scholars still perform simple cholecystectomy on stage II patients, and blindly perform extended radical resection of gallbladder cancer on patients who cannot complete R0 radical resection.

2. Early and unexpected gallbladder cancer

T1a stage may be the most common after laparoscopic cholecystectomy. Lymph node metastasis is rare in these patients. The 5-year survival rate of patients with simple cholecystectomy is as high as 85-100% if the resection margin is negative. Therefore, simple cholecystectomy for T1a gallbladder cancer is an undisputed treatment strategy among scholars at home and abroad.

T1b stage tumors invade the muscularis mucosa, and metastasis is rare, but most scholars still advocate that regional lymph node dissection should be performed. There are two reasons for this: first, there is no serosa on the gallbladder bed, and second, the gallbladder wall has a rich lymphatic network. Cancer cells may have very early lymphatic metastasis, leading to postoperative recurrence. The one-year survival rate of patients undergoing simple cholecystectomy at this stage is only 50-80%, and further surgery can improve the prognosis. Of course, there are also a few scholars who insist that as long as the gallbladder resection margin is pathologically negative, there is no need for reoperation, and the survival rate of reoperation is not statistically significant compared with simple cholecystectomy. There are few domestic literatures involving the analysis of patients with T1b gallbladder cancer, but most experts believe that patients with suspected positive postoperative margins should undergo a second operation as soon as possible.

This group of patients often undergo laparoscopic cholecystectomy, and is more common in patients with a long history of cholecystitis, thickened gallbladder wall, and larger stones and gallbladder polyps. Due to the damage of the gallbladder during the operation, some patients may have tumor implantation and metastasis in the abdominal cavity and puncture tract after surgery, which is quite difficult to treat and has a poor prognosis. Therefore, the preoperative examination of cholecystectomy should be as complete as possible, and laparotomy should be performed on patients with suspected gallbladder cancer. It has been reported that laparoscopic resection promotes abdominal implantation and metastasis in patients with gallbladder cancer after surgery. Whether it is from the perspective of accidental gallbladder cancer requiring reoperation or laparoscopic surgery may promote gallbladder cancer implantation and metastasis, there is reason to support that these patients should choose laparotomy as much as possible for cholecystectomy with a tendency to gallbladder cancer.

Patients with gallbladder cancer found after laparoscopic surgery should be treated according to the pathological staging of the postoperative lesions. At present, most scholars support that patients before stage T1a do not need to undergo a second surgery after complete cholecystectomy, and patients at stage T1b and above should still undergo radical resection as soon as possible. However, some scholars believe that as long as gallbladder cancer is located on the free serosal surface and does not invade surrounding organs, whether it invades the entire layer or not, it does not need to be radically cleaned again. Most scholars believe that the scope of resection for early gallbladder cancer is not enough for simple cholecystectomy. Chen Fei et al. reported that the 1, 3, 5, and 8-year survival rates of 7 patients with early unexpected gallbladder cancer who underwent simple cholecystectomy (5 cases were Nevin stage I and 2 cases were Nevin stage II) were significantly different from those of 17 patients who underwent radical surgery (100%, 94.1%, 70.6%, 35.3%). One of the patients in stage Nevin I developed jaundice 3 months after surgery, and reoperation could not cure it. Lu Junhua et al. also hold the same view. Tian Hua et al.'s research data showed that the resection rate of radical surgery in the group of unexpected gallbladder cancer was 72.2%, while the resection rate of radical surgery in the group of preoperatively diagnosed gallbladder cancer was only 39.5%. The cumulative 5-year survival rates after radical surgery in the two groups were 54.6% and 23.5%, respectively. The median survival time of 61 cases of gallbladder malignant tumors in the two groups after radical surgery and palliative surgery was 43.3 months and 10.5 months, respectively. Based on this, it is believed that the overall prognosis of unexpected gallbladder cancer is better than that of preoperatively diagnosed gallbladder malignant tumors, and active reoperation radical surgery can improve the prognosis of patients with unexpected gallbladder cancer.