What are the early symptoms of gallbladder cancer? Can gallbladder cancer be cured?

Among the malignant tumors of the gallbladder, carcinoma of the gallbladder ranks first, and there are other types, such as sarcoma, carcinoid, primary malignant melanoma, giant cell adenocarcinoma, etc. Since the latter are rare, this chapter mainly discusses primary gallbladder cancer. In the past, it was considered a relatively rare malignant tumor. No matter what method was used for treatment, the course of the disease still progressed rapidly and eventually led to death.

Women are 2 to 4 times more likely to develop the disease than men. It is more common in people aged 50 to 70. Early diagnosis and appropriate treatment methods are of great significance to the prognosis of this disease.

1. Gallbladder Cancer Symptoms

Gallbladder cancer has no specific clinical manifestations in the early stage, or only has symptoms of chronic cholecystitis, and early diagnosis is very difficult. Once persistent pain, mass, jaundice, etc. appear in the upper abdomen, the disease has reached the late stage, and various examinations also show abnormalities. Therefore, for patients with discomfort or pain in the gallbladder area, especially middle-aged and elderly patients over 50 years old with gallstones, inflammation, and polyps, regular B-ultrasound examinations should be performed to obtain an early and clear diagnosis.

1. Right upper abdominal pain

Most cases are persistent pain in the right upper abdomen, which may be aggravated paroxysmically and radiate to the right shoulder and waist and back. This symptom accounts for 84%. Since gallbladder cancer often coexists with gallbladder stones and inflammation, the pain is similar to that of calculous cholecystitis, starting with discomfort in the right upper abdomen, followed by persistent dull pain or dull pain, sometimes accompanied by paroxysmal severe pain and radiating to the right shoulder.

2. Digestive tract symptoms

The vast majority (90%) experience indigestion, aversion to greasy food, belching, and decreased appetite, which is due to the gallbladder's inability to digest fat. Nausea and vomiting are also quite common, and there is often a loss of appetite.

3. Jaundice

Due to the spread of cancer, about 1/3 to 1/2 of patients develop jaundice. Jaundice is the first symptom in a few patients, and most jaundice occurs after pain. Jaundice is persistent and progressive, and a few patients show intermittent jaundice. Jaundice often appears in the late stage of the disease, accounting for 36.5%, mostly due to cancer tissue invading the bile duct and causing malignant obstruction. It is also accompanied by weight loss, fatigue, and even cachexia, yellowing of the skin and mucous membranes, and difficult-to-treat skin itching.

4. Chills and fever

It often occurs in the late stage of cancer. 25.9% of patients develop fever, and the high fever may persist.

5. Lump in the right upper abdomen

When the disease develops to the late stage, a mass appears in the right upper abdomen or upper abdomen, accounting for 54.5%. One is that the tumor grows rapidly, blocking the bile duct and causing the gallbladder to swell; the other is that it invades the duodenum and causes obstruction symptoms; in addition, if it invades the liver, stomach, pancreas, etc., masses may also appear in the corresponding parts.

2. Physical signs

1. Jaundice

It manifests as yellowing of the mucous membranes and skin. Severe jaundice is mostly obstructive. Once jaundice occurs, the disease is usually in the late stage.

2.Right upper abdominal mass

A relatively smooth and enlarged gallbladder can be felt in the right upper abdomen. When there is no adhesion to the surrounding tissue, it is highly mobile. When there is adhesion to the surrounding tissue, several lumps can be felt, and sometimes an enlarged liver or a mass of duodenal obstruction can be felt. In nearly half of the cases, a mass can be felt in the gallbladder area in the right upper abdomen at the time of initial diagnosis. Some parts are hard and have a nodular feel. This mass is the gallbladder. Occasionally, due to obstruction of the cystic duct, the gallbladder may have water accumulation or abscess formation, and tenderness in the gallbladder area and rebound pain may occur. Its signs are very similar to those of acute cholecystitis or obstructive cholangitis.

3. Weight loss

Most cases present with gradual emaciation, weight loss, fatigue, and cachexia.

4. Signs caused by metastasis

In some cases, metastatic lymph nodes can be felt above the clavicle, and metastatic masses may also appear in the breast, etc. In advanced cases, there may be gastrointestinal bleeding, ascites, and liver failure due to portal vein compression.

Comprehensive manifestations of five major types of diseases Gallbladder cancer has an insidious onset and no specific manifestations, but it is not without rules. The clinical manifestations from high to low frequency are abdominal pain, nausea and vomiting, jaundice and weight loss. Clinically, its symptom group can be classified as a comprehensive manifestation of five major types of diseases: ① Acute cholecystitis: Some cases have a history of short-term right upper abdominal pain, nausea, vomiting, fever and palpitations, suggesting acute cholecystitis. About 1% of cases that undergo surgery for acute cholecystitis have gallbladder cancer. At this time, the lesions are often in the early stage, with a high resection rate and a long survival period. ② Chronic cholecystitis: Many patients with primary gallbladder cancer have symptoms similar to those of chronic cholecystitis, which are difficult to distinguish. Be highly vigilant about benign lesions combined with gallbladder cancer, or benign lesions developing into gallbladder cancer. ③ Malignant tumors of the biliary tract: Some patients may have jaundice, weight loss, poor general condition, right upper abdominal pain, etc. Tumor lesions are often late and the efficacy is poor. ④Signs of extra-biliary malignancies: A few cases may present with nausea, weight loss, general weakness, fistula formation or invasion of adjacent organs. This type of tumor is often not resectable. ⑤Manifestations of extra-biliary benign lesions: Rare, such as gastrointestinal bleeding or upper gastrointestinal obstruction.

(1) Symptoms of chronic cholecystitis

30% to 50% of cases have symptoms of chronic cholecystitis or gallstones, such as long-term right upper abdominal pain, which are difficult to differentiate. Patients with chronic cholecystitis or gallstones who are over 40 years old and have recent right upper abdominal pain that becomes persistent or progressively worse and have obvious symptoms of digestive disorders; patients over 40 years old with asymptomatic gallstones, especially those with larger single gallstones, who have recent persistent dull or dull pain in the right upper abdomen; patients with a short history of chronic cholecystitis who have obvious changes in local pain and systemic conditions; patients with gallstones or chronic cholecystitis who have recently developed obstructive jaundice or palpable masses in the right upper abdomen should all be highly suspected of gallbladder cancer and should undergo further examinations to confirm the diagnosis.

(2) Symptoms of acute cholecystitis

It accounts for 10% to 16% of gallbladder cancer. Most of these patients have acute cholecystitis or gallbladder abscess caused by tumors in the neck of the gallbladder or incarcerated stones. The resection rate and survival rate of these patients are relatively high, with a resection rate of 70%, but it is almost impossible to diagnose before surgery. Some patients are misdiagnosed as acute cholecystitis due to drug treatment or simple cholecystostomy. Therefore, for the sudden onset of acute cholecystitis in the elderly, especially those who have no biliary system diseases in the past, special attention should be paid to the possibility of gallbladder cancer and early surgical treatment should be sought. When cholecystostomy is necessary due to the condition, the gallbladder cavity should also be carefully examined to rule out gallbladder cancer.

(3) Symptoms of obstructive jaundice

Some patients seek medical treatment with jaundice as the main symptom. About 40% of gallbladder cancer patients have jaundice. The appearance of jaundice indicates that the tumor has invaded the bile duct or is accompanied by common bile duct stones. Both of these situations can be encountered in the resection of gallbladder cancer.

(4) Mass in the right upper abdomen

Tumors or stones blocking the gallbladder neck can cause gallbladder fluid accumulation, pus accumulation, and gallbladder swelling. This smooth and elastic mass can usually be removed and has a good prognosis. However, hard, nodular, and rough masses are incurable advanced cancers.

(5) Others

Hepatomegaly, weight loss, ascites, and anemia may all be late signs of gallbladder cancer, indicating that there has been liver metastasis or gastroduodenal invasion and that surgical resection may not be possible.

The clinical manifestations of gallbladder cancer lack specificity, and its early signs are often masked by cholelithiasis and its complications. Except for the first attack of acute cholecystitis, it is generally difficult to make an early clinical diagnosis based on clinical manifestations. According to statistics, the preoperative diagnosis rate is 29.6%, and most of them are in the late stage. Therefore, in order to achieve asymptomatic and early diagnosis, it is necessary to closely follow up high-risk groups, such as patients with static gallstones, gallbladder polyps, and gallbladder adenomyosis, and actively treat them when necessary to prevent gallbladder cancer. In recent years, with the development of imaging diagnostic technology, the number of early diagnosed cases of gallbladder cancer has tended to increase. Anyone with any of the following manifestations should consider the possibility of gallbladder cancer:

1. Female patients aged 40 and above with a history of chronic cholecystitis or gallstones and recurrent symptoms.

2. Patients with jaundice, loss of appetite, general fatigue, weight loss, and a mass felt in the right upper abdomen.

3. Pain in the right upper abdomen or pit of the stomach that is not responsive to general liver or stomach disease treatment.

4. Digestive dysfunction, such as nausea, vomiting, anorexia, aversion to oil, loose stools, etc., for those who are not responding to general symptomatic treatment.

For the diagnosis of gallbladder cancer, Japanese scholars proposed the following diagnostic procedure (Figure 3), which can be used for reference:

Primary gallbladder cancer has no specific symptoms and signs in the early stage. Most patients have a history of chronic cholecystitis and cholelithiasis. It often presents as the clinical features of existing gallbladder or liver diseases, or even stomach diseases, and is easily overlooked. When the cancer reaches the late stage, its symptoms become obvious and gradually worsen.

Staging of Gallbladder Cancer

(1) Nevin staging method: Nevin staging method is often used in the literature, namely:

Stage I: The tumor is confined to the gallbladder mucosa.

Stage II: invasion into the muscular layer.

Stage III: Invasion of the entire gallbladder wall.

Stage IV: invasion of all layers of the tumor with metastasis to surrounding lymph nodes.

Stage V: Direct invasion of the liver or metastasis to other organs.

(2) The American Cancer Foundation stages are:

Tis: carcinoma in situ.

T1: invasion into the muscular layer.

T2: invasion into the serosa.

T3: Invasion of tissues outside the gallbladder or an adjacent organ.

T4: Liver metastasis larger than 2 cm or metastasis to more than two organs.

(3) Due to different staging standards for early stage cancer, there is no clear definition in the literature on what constitutes early and late stages. It is generally believed that the definition of early stage cancer should include:

①No lymph node metastasis.

② There is no lymphatic vessel, venous or nerve metastasis.

③The depth of cancer cell infiltration is limited to the mucosal layer or submucosal layer.

This definition does not include muscle-invasive carcinoma of the gallbladder.

①No lymph node metastasis.

② There is no lymphatic vessel, venous or nerve metastasis.

③The depth of cancer cell infiltration is limited to the mucosal layer or submucosal layer.

This definition does not include muscle-invasive carcinoma of the gallbladder.

Cholelithiasis (25%): Patients with gallbladder cancer often have concurrent gallstones, with a prevalence of 70% to 80% in Europe and the United States, 58.8% in Japan, and 80% in my country. Gallbladder cancer often develops in the neck of the gallbladder, which is easily hit by gallstones, and often occurs in patients who have had gallstones for more than 10 years. Therefore, it is believed that gallstones are closely related to gallbladder cancer. For patients with gallstones greater than 3 cm in diameter, the risk of gallbladder cancer is 10 times greater than that for patients with gallstones less than 1 cm in diameter. Some people believe that gallstones contain carcinogenic factors, but there is a lack of definite evidence, and the incidence of gallbladder cancer in patients with cholelithiasis is only 1% to 2%. Therefore, it is not clear whether there is a clear causal relationship between gallstones and gallbladder cancer.

Strauch counted 18 articles and found that the relationship between gallbladder cancer and gallstones was 54.3% to 96.9%. Jones reported that 3/4 of gallbladder cancers were accompanied by gallstones. Balaroutsos et al. reported that 77% of gallbladder cancer cases were accompanied by gallstones. Priehler and Crichlow reviewed 2,000 cases of gallbladder cancer and found that 73.9% of them were accompanied by gallstones. Animal experiments have shown that methylcholanthrene prepared from bile acid, deoxycholic acid, and cholesterol can form gallbladder cancer when implanted into the gallbladder of cats. Lowenfels believed that the occurrence of biliary tumors was related to the obstruction and infection of these organs, which caused bile acid to be converted into more active substances. Hill et al. found Clostridium in 2/3 of gallstones. This bacterium can deoxidize bile acid and convert it into deoxycholic acid and lithocholic acid, both of which are substances related to polycyclic aromatic hydrocarbon carcinogens. Gallstones can cause chronic inflammation. The porcelain gallbladder (procellaneous gallbladder) with calcified gallbladder has a high rate of malignant transformation. However, it has not been fully proven whether the long-term chronic stimulation of gallstones can induce gallbladder cancer. It can only be said that gallstones can increase the incidence of gallbladder cancer. The incidence of gallbladder cancer in American Indian women with cholelithiasis for 20 years increased from 0.13% to 1.5%. Nervi et al. used the Logistic regression model to calculate that the incidence of gallbladder cancer in patients with gallstones is 7 times higher than that in those without stones.

40% to 50% of patients with gallbladder cancer have chronic gallbladder inflammation. Some people studied cholecystectomy specimens and found that the rates of atypical cell proliferation and malignant transformation were higher in the group with severe chronic gallbladder inflammation than in the group with mild chronic gallbladder inflammation; there was a high rate of intestinal metaplasia in non-cancerous areas; and there was a tumor structure similar to the intestinal epithelium in the cancer foci. Therefore, it is believed that intestinal metaplasia is an important lesion for the occurrence of cancer. The occurrence of gallbladder cancer may be a process of development from normal gallbladder mucosa to chronic cholecystitis (including stones) to intestinal metaplasia to differentiated gallbladder cancer (intestinal type cancer).

Gallbladder adenoma (10%): Sawyer reported 29 cases of benign gallbladder tumors, of which 4 were malignant. He reviewed the literature of the past 20 years and believed that gallbladder adenoma is a precancerous lesion. Gallbladder adenomas are mostly solitary and pedunculated, with a canceration rate of about 10%. If combined with gallstones, the risk of canceration increases. Studies have found that those with a diameter of less than 12 mm are mostly benign adenomas, and those with a diameter of more than 12 mm are mostly malignant lesions. All carcinomas in situ and 19% of invasive carcinomas have adenomatous components, so it is believed that adenomas have the potential to become cancerous.

Yamagiwa and Tomiyama studied the histological examination of 1,000 gallbladders and found that 4% of those without gallstones had intestinal metaplasia. In those with gallstones, 30.6% had intestinal metaplasia, 69.8% had dysplasia, and 61.1% had gallbladder cancer. Among the 36 cases of gallbladder cancer tissues, dysplasia and adenoma accounted for 22.2% and 8.3%, respectively. Therefore, it is believed that the order of onset from intestinal metaplasia to dysplasia to gallbladder cancer may be significant.

Adenomyosis of the gallbladder: It was previously believed that adenomyosis of the gallbladder had no possibility of malignant transformation, but in recent years there have been reports of patients with adenomyosis of the gallbladder developing gallbladder cancer. It has now been confirmed as a precancerous lesion of gallbladder cancer.

Abnormal confluence of the pancreatic and bile ducts (5%): Kinoshita and Nagata studied that when the common channel of the pancreatic and bile ducts exceeds 15 mm, pancreaticobiliary reflux occurs, which is called abnormal confluence of the pancreatic and bile ducts. Many authors have pointed out that abnormal confluence of the pancreatic and bile ducts increases the incidence of gallbladder cancer. When the confluence of the pancreatic and bile ducts is malformed, long-term reflux of pancreatic juice causes continuous destruction and repeated regeneration of the gallbladder mucosa. Cancer may occur in this process. It has been reported that ERCP examination found that 16% of patients with gallbladder cancer had combined malformation of the pancreatic-biliary confluence. Kimura et al. reported 65 cases of gallbladder cancer confirmed by angiography. At the same time, 65 cases of abnormal confluence of the pancreatic and bile ducts were observed, and 16.7% of them had combined gallbladder cancer. The control group had 641 cases with normal confluence of the pancreatic and bile ducts and the incidence of gallbladder cancer was 8%. Another group reported that the incidence of gallbladder cancer was 25% in patients with abnormal confluence of the pancreatic and bile ducts, and the incidence of gallbladder cancer was 1.9% in 635 cases in the normal confluence group.

Other factors (5%): In addition, Ritchie et al. reported that chronic ulcerative colitis is often accompanied by gallbladder cancer. The incidence of gallbladder cancer is increased in patients with Mirizzi syndrome, which may also be one of the causes. There are reports that the onset of gallbladder cancer is related to abnormalities of the cystic duct or congenital bile duct dilatation.

The cause of gallbladder cancer is still unclear. Clinical observation shows that gallbladder cancer often coexists with benign gallbladder diseases, most commonly with gallstones. Most people believe that chronic stimulation of gallstones is an important pathogenic factor. Moosa pointed out that 3.3% to 50% of patients develop gallbladder cancer 5 to 20 years after "hidden stones". Domestic bulk data reports that 20% to 82.6% of gallbladder cancers are accompanied by gallstones, and foreign reports show that the rate is as high as 54.3% to 100%. The occurrence of cancer is closely related to the size of the stones. The probability of cancer occurring in patients with stones less than 10 mm in diameter is 1.0, in patients with stones between 20 and 22 mm in diameter it is 2.4, and in patients with stones over 30 mm in diameter the probability can be as high as 10%. Others have suggested that the occurrence of gallbladder cancer may be related to the presence of a malformation at the junction of the lower end of the common bile duct and the main pancreatic duct. This malformation allows pancreatic juice to enter the bile duct, increasing the concentration of pancreatic juice in the bile, causing chronic inflammation of the gallbladder, mucosal changes, and finally cancer. The cause of gallbladder cancer is still unclear.

Pathogenesis

There are many different tissue types of gallbladder cancer, but none of them has a fixed growth pattern and special clinical manifestations. The vast majority of gallbladder cancers are adenocarcinomas, accounting for about 80%, of which 60% are scirrhous adenocarcinomas, 25% are papillary adenocarcinomas, 15% are mucinous adenocarcinomas, and the rest are undifferentiated carcinomas (6%), squamous cell carcinomas (3%), mixed tumors or acanthoma (1%), and other rare tumors include carcinoids, sarcomas, melanomas, and lymphomas.

Macroscopic observation often shows diffuse thickening of the gallbladder wall and invasion of adjacent organs. Occasionally, papillary protrusions are seen growing into the gallbladder cavity. The spread of gallbladder cancer is mainly local infiltration of the liver and surrounding organs such as the duodenum, colon, and anterior abdominal wall. If the tumor of the gallbladder neck or Hartmann's pouch directly infiltrates the common hepatic duct, it is difficult to distinguish it from cholangiocarcinoma in clinical manifestations and radiological imaging examinations. Early lesions can directly infiltrate the gallbladder fossa or spread through the gallbladder vein along the gallbladder neck and invade the quadratic lobe of the liver. The gallbladder wall is rich in lymphocytes. The gallbladder is conducive to the early spread of the tumor to the cystic duct, common bile duct and lymph nodes around the pancreaticoduodenal area. Distant metastasis and transabdominal dissemination are not seen until the late stage of the tumor. Clinically, only 10% of patients are found to have tumors confined to the gallbladder during cholecystectomy due to cholelithiasis. Another 15% have already invaded the gallbladder fossa or surrounding lymph nodes in the early stage. If extended radical surgery is performed at this stage, there is still a possibility of cure. Piehler et al. (1978) collected 984 cases of gallbladder cancer reported in the literature, of which 69% invaded the liver and 45% involved regional lymph nodes.

75% of gallbladder cancers can directly invade surrounding organs, with the frequency of occurrence being liver, bile duct, pancreas, stomach, duodenum, omentum and colon. 60% have lymph node metastasis, about 15% have distant metastasis, and less than 20% have peritoneal metastasis. Spread along the nerve sheath is one of the characteristics of hepatobiliary system cancer. Nearly 90% of patients with advanced gallbladder cancer have nerve invasion, which is the main cause of pain caused by this disease.

Pathological staging of gallbladder cancer: In 1976, Nevin et al. first proposed a clinical pathological staging and grading scheme for primary gallbladder cancer, which was based on the scope of infiltration, growth and spread of gallbladder cancer tissue and the degree of cell differentiation. Due to its simplicity and practicality, it was quickly recognized and widely adopted by a large number of surgical scholars. It is specifically divided into 5 stages and 3 grades. The scheme is as follows: Staging: Stage I, cancer tissue is limited to the gallbladder mucosa; Stage II, cancer tissue invades the gallbladder mucosa and muscular layer; Stage III, cancer tissue invades the entire layer of the gallbladder wall, namely the mucosa, muscular layer and serosa; Stage IV, cancer tissue invades the entire layer of the gallbladder wall and has lymph node metastasis; Stage V, cancer tissue directly invades the liver or has liver metastasis, or has metastasis to any organ. Grading: Grade I, well-differentiated cancer; Grade II, moderately differentiated cancer; Grade III, poorly differentiated cancer. Staging and grading are independently related to prognosis, and the sum of staging and grading has a significant correlation with prognosis. The higher the value, the worse the prognosis.

The International Union Against Cancer (UICC) announced the unified TNM staging standard for gallbladder cancer in 1995, which has become an important reference for comprehensively measuring the condition, determining treatment strategies and evaluating prognosis. Studies have shown that after radical surgery for gallbladder cancer, there is no significant difference in the survival curves of stage I and II tumors, and the cumulative survival time is significantly longer than that of stage III and IV patients. There are many factors that affect the prognosis of gallbladder cancer, such as tissue grading, pathological type, etc., but pathological staging is the most important. In addition, correctly determining the TNM staging of gallbladder cancer is very necessary when formulating surgical methods and auxiliary treatment plans.

This disease is difficult to diagnose in the early stages, so the prognosis is poor. The 5-year survival rate after surgery is 0-7%, with occasional reports of over 10%. 80% of patients die within 1 year after diagnosis.

In 1992, Heason collected data on 3038 cases of gallbladder cancer and found that the patient's age, gender, weight, race, geographical environment and diet were all related to the incidence of gallbladder cancer. The age of onset of gallbladder cancer was concentrated between 40 and 60 years old, and was higher in women; obesity was an important risk factor for cholelithiasis; excessive intake of greasy food, monosaccharides and disaccharides would increase the risk of gallbladder cancer. These research results have guiding significance for the prevention of gallbladder cancer.

For middle-aged and older patients, especially female patients, with chronic atrophic cholecystitis, chronic calcific cholecystitis, uncured gallstones, adenomatous polyps of the gallbladder, especially those with polyps >10mm, wide base, polyps with stones, and inflammation, cholecystectomy should be performed as soon as possible. In view of the relationship between benign gallbladder diseases and gallbladder cancer, it is generally believed that preventive measures should be taken for people at high risk of gallbladder cancer:

① Patients over 40 years old with obvious symptoms of cholecystitis, gallstones, especially those with a stone diameter greater than 3 cm, obvious thickening and atrophy of the gallbladder wall, or "porcelainization" should have their gallbladder removed.

② For patients who have undergone cholecystostomy due to acute cholecystitis, cholelithiasis, or necrosis, early cholecystectomy should be performed if there are no contraindications.

③ Benign tumors of the gallbladder, such as adenoma and adenomyoma, should be checked regularly or the gallbladder should be removed in a timely manner.

④ For those with cystic duct malformation, abnormal pancreaticobiliary duct junction, congenital bile duct dilatation, long-term ulcerative colitis, and long-term exposure to chemical carcinogens, changes in the gallbladder should be observed regularly.

Treatment Overview Department of Surgery: Hepatobiliary Surgery

Treatment: Surgery, medication

Treatment period: 3 months

Cure rate: Poor prognosis. If the tumor is confined to the gallbladder, the 2-year survival rate can reach 45%.

Commonly used drugs: Xiaoaiping tablets and Cidan capsules

Treatment costs: The charging standards vary from hospital to hospital. The city's top three hospitals charge about RMB 10,000 to 30,000.

Western medicine treatment of gallbladder cancer

Surgical treatment:

Gallbladder cancer should be treated with a comprehensive treatment with surgery as the main treatment. General treatment includes systemic support, nutritional supplements, and increased diet. When symptoms are related to diet, a low-fat diet can be taken. Pain relief is the same as general treatment. If the pain is difficult to relieve, procaine can be given intravenously or morphine can be used.

1. Surgical treatment: Gallbladder cancer is mainly treated with surgery, but due to the insidious onset, no specific symptoms, and difficulty in early diagnosis, few patients can undergo surgical resection, with domestic literature reporting 50%. Even fewer patients can undergo radical surgery, only 20.2%. Even if the lesion has been removed, the average survival time after surgery is only 8.4 months, and nearly 90% of patients die within 1 year after surgery. The 5-year survival rate is less than 5% (0% to 10%), and some reports are 14.5%. In recent years, surgical resection of lesions plus radionuclide intraoperative irradiation for advanced patients has been carried out abroad, which may improve their prognosis and quality of life. Gallbladder cancer surgery can also be divided into palliative surgery, radical surgery, and extended radical surgery. Palliative surgery refers to the use of local resection of gallbladder masses or various drainage surgeries to improve patient symptoms when the tumor is no longer curable. Radical surgery should have different meanings depending on the early or late stage of the disease. For carcinoma in situ or early cancer limited to the mucosa, simple cholecystectomy can be considered a radical cure. For patients who have invaded the muscle layer or the entire gallbladder wall, it is necessary to remove 2 to 3 cm of liver tissue and the cystic duct and the lymph nodes around the common hepatic duct to be considered a radical cure. For advanced patients whose liver has been invaded and whose surrounding lymph nodes have metastasized, extended radical surgery is the only option. Extended radical surgery refers to the removal and reconstruction of the right liver lobe, pancreatic head, duodenum, and blood vessels when there is metastasis to the regional lymph nodes or adjacent organs.

Occult gallbladder cancer refers to a condition that has not been diagnosed before or during surgery, but is diagnosed as gallbladder cancer by pathological examination after cholecystectomy for a "benign" disease. Since occult gallbladder cancer is diagnosed after surgery, the question is whether radical surgery is needed again. For patients whose postoperative pathology confirms that the cancer has only invaded the mucosal layer or the muscular layer, a complete cholecystectomy alone is sufficient to achieve the goal of radical cure, and a second radical surgery is not necessary. Since the location of the cancer in the gallbladder neck, especially the cystic duct, is close to the gallbladder triangle, lymph node metastasis is prone to occur earlier. Therefore, no matter which layer of the gallbladder wall is invaded, lymph node dissection around the hepatoduodenal ligament should be performed again. A second radical surgery should also be performed for occult gallbladder cancer that has infiltrated beyond the muscular layer, has a positive resection margin, and has a positive gallbladder triangle lymph node biopsy.

For advanced cases that cannot be cured, the principle of surgery is to relieve pain and improve the quality of life. The prominent problem of advanced gallbladder cancer is obstructive jaundice caused by cancer invasion of the bile duct. Internal drainage should be considered as much as possible during surgery. The methods of internal drainage include bile duct jejunostomy, bridging internal drainage, etc. For cases with extremely poor systemic conditions, external drainage by catheterization can also be performed. At present, memory alloy stents have been successfully used in biliary surgery. For patients with bile duct obstruction, stents are placed during surgery to support the bile duct, which can drain the bile.

For patients after surgery, radiotherapy and/or chemotherapy as well as traditional Chinese medicine should be used as appropriate to prolong survival. For patients with liver metastases that have been resected or cannot be resected, hepatic artery and/or portal vein chemoembolization can be used for treatment, but the number of cases is small and needs further verification.

(1) Radical surgery: Perform radical surgery according to the extent of the lesion and the biological characteristics of the tumor. Adson reported that 63% of the resected cases still did not meet the requirements of radical cure. If the lesion is still limited to the liver adjacent to the gallbladder and the lymph node metastasis does not exceed the second station, it should be considered as a curable gallbladder cancer and a reasonable radical surgery should be performed.

① Simple cholecystectomy: If the cancer is limited to the mucosal layer, simple cholecystectomy can achieve the purpose of radical cure without lymph node dissection. This situation is mostly due to benign lesions of the gallbladder, which are discovered during intraoperative or postoperative pathological examination. Some people believe that simple cholecystectomy can be performed for stages I and II of the Nevin classification, especially papillary carcinoma. Berhdam reported that if gallbladder cancer invades the mucosa and submucosal layer, simple cholecystectomy is required, and the 5-year survival rate after surgery can reach 64%, and the 10-year survival rate is 44%.

② Patients whose regional lymph node dissection invades the muscular layer and the entire layer of the gallbladder often have gallbladder lymph node metastasis. Lymph node dissection is also required for highly malignant pathological types such as mucinous adenocarcinoma and undifferentiated carcinoma. The scope of dissection includes the first and second station lymph nodes, with the right edge of the portal vein as the boundary, and the lymph nodes in the hepatoduodenal ligament are completely removed. Then the duodenum is turned up to remove the pancreaticoduodenal and lower common bile duct lymph nodes.

③ Liver wedge resection: If the lesion invades the entire layer of the gallbladder or the adjacent liver, a liver wedge resection should be performed. A 1.5-4 cm liver wedge resection should be performed along the edge of the gallbladder bed according to the extent of the lesion.

④ Right hepatic lobectomy and hepatic segment resection: used for patients with a large range of liver bed infiltration and direct infiltration of the hepatic duct. 50 years ago, some people began to use right hemihepatectomy to treat gallbladder cancer. More than 20 cases were reported in the literature, and only one case survived for 5 years, indicating that this operation cannot improve the survival rate. Bismuth used liver segment resection to treat 5 cases of Nevin stage IV. Except for one case with residual cancer who recurred and died 2 years after surgery, the other 4 cases are still alive, and 3 have survived for more than 2 years. The surgical mortality rate is also low, and the long-term efficacy is good. Therefore, for cases with metastasis to the adjacent liver, especially gallbladder ampulla cancer, liver segment resection Ⅳ and Ⅴ is a more reasonable extended surgical method. ⑤ Partial resection of other adjacent organs: If the gastric antrum, duodenum, and hepatic flexure of the colon are invaded, the affected organs can be removed as a whole together with the gallbladder.

⑥ Partial resection of the extrahepatic bile duct: For lesions located in the neck of the gallbladder or extending to the cystic duct, as well as papillary carcinoma, special attention should be paid to exploring the extrahepatic bile duct. If the bile duct is found to be invaded, it should be removed at the same time.

Gallbladder cancer discovered during or after cholecystostomy should undergo radical surgery as soon as possible if necessary, and the resection range should include the tissues around the abdominal wall sinus. When there is a gastrointestinal fistula, the adjacent organs that are connected should be removed at the same time; acute perforated gallbladder cancer should be flushed with distilled water and anticancer drugs at the end of the operation. Gallbladder cancer diagnosed by postoperative pathology is called occult gallbladder cancer by some people. In fact, gallbladder cancer discovered by postoperative pathology is not necessarily early. Therefore, it is very important to emphasize the routine dissection and examination of the removed gallbladder during surgery. For gallbladder cancer reported by postoperative pathology, except for stage I, reoperation should be performed as soon as possible according to the situation, with regional lymph node dissection or liver wedge resection. Some people believe that such patients can undergo radiotherapy for 2 to 3 months before radical surgery.

In the past, it was believed that patients with lesions beyond the gallbladder and invading the adjacent liver, liver hilum or extrahepatic bile duct with metastatic masses and jaundice, and lymph node metastasis to the third station, were not suitable for extended radical resection. Currently, some individuals use cholecystectomy and bile duct resection combined with right hepatic lobectomy, cholecystectomy combined with pancreaticoduodenectomy, right hepatic lobectomy plus pancreaticoduodenectomy combined with portal vein and hepatic artery resection and reconstruction to treat advanced gallbladder cancer. However, it is difficult to evaluate due to the small number of cases.

(2) Palliative surgery:

① Palliative cholecystectomy: When the lesion is beyond the scope of radical cure, palliative cholecystectomy can be performed to relieve symptoms; palliative cholecystectomy should also be performed when the patient is too old, suffers from other medical diseases, or has a serious infection in the gallbladder, etc., when it is not appropriate to expand the scope of surgery.

② Biliary drainage: including biliary enteric drainage or stent tube drainage, external bile duct drainage and PTCD external drainage, etc., which are used for patients with obstructive jaundice.

A nationwide survey of 1,098 cases of extrahepatic biliary cancer showed that surgical resection had a significantly better prognosis than simple external drainage, while drainage had no significant difference compared with non-surgical surgery. In some cases with lower malignancy and slower progression, palliative surgery can extend survival.

Among digestive tract cancers, gallbladder cancer has the lowest resection rate and long-term survival rate, mainly because most cases are in the late stage. Early diagnosis is extremely important.

Other special treatments:

(1) Radiotherapy: Gallbladder cancer is sensitive to radiotherapy. Early-stage patients have a greater chance of local recurrence after surgery, which is also the main cause of death. Therefore, some authors advocate that radiotherapy should be performed after radical surgery. A group of stage IV patients received intraoperative internal irradiation therapy (IORT) combined with postoperative external irradiation therapy (ERT). During surgery, the electron beam was mainly used to irradiate the liver resection margin, the hepatoduodenal ligament and other places where residual cancer lesions may remain. A single dose of 20 to 30 Gy was given during surgery, with good efficacy. The 3-year cumulative survival rate was 10.1%, while that of the control group was 0. Radiotherapy for patients with advanced disease who cannot undergo palliative resection or resection requires a larger dose of radiation. Some people advocate giving 70 Gy, which should be completed within 7 to 8 weeks, which may prolong survival time.

In order to prevent and reduce local recurrence, radiotherapy can be used as an adjuvant treatment for gallbladder cancer surgery. Some scholars have conducted preoperative radiotherapy with a total dose of 30Gy on a group of gallbladder cancer patients. The results showed that the surgical resection rate of the group receiving preoperative radiotherapy was higher than that of the control group, and it did not increase the fragility of tissues and the amount of intraoperative bleeding. However, it is difficult to make a relatively accurate diagnosis of the size of the gallbladder cancer tumor and the range involved before surgery, so the dose of radiotherapy is difficult to control. Intraoperative radiotherapy can make a correct judgment on the size of the tumor and the range involved, and has the advantages of accurate positioning and reducing or avoiding radiation damage to normal tissues and organs. The experience of the First Hospital of Xi'an Jiaotong University is that a one-time radiation dose of 20Gy to the tumor area during surgery for 10 to 15 minutes can improve the patient's prognosis. Postoperative radiotherapy is the most commonly used in clinical practice. The location and size of the tumor are determined during surgery, and the area of ​​postoperative radiotherapy is marked with a metal clip. It usually starts 4 to 5 weeks after surgery, and the external irradiation lasts for 4 to 5 weeks, with a total dose of 40 to 50Gy. According to the reports of postoperative radiotherapy results from various institutions, the median survival of patients receiving postoperative radiotherapy is higher than that of the control group, especially for patients with Nevin stage III and IV or non-radical resection, the relative efficacy is more obvious. In recent years, there have also been reports that the combination of intracavitary irradiation and external irradiation of PTCD has a certain effect.

(2) Chemotherapy: Gallbladder cancer is insensitive to various chemotherapy drugs and is mostly used for adjuvant therapy after surgery. There is currently no unified chemotherapy regimen, and the chemotherapy regimens that have been used are not ideal. By measuring the P-glycoprotein content in normal gallbladder and gallbladder cancer specimens, it was found that the gallbladder itself is an organ rich in P-glycoprotein, so it is necessary to rationally select chemotherapy drugs. Commonly used chemotherapy drugs include fluorouracil (5-FU), cyclohexylnitrosourea (Me-CCNU), doxorubicin (adriamycin), mitomycin, carmustine (carboplatin), etc. Combined use has a certain effect and can be tried when there is no other choice. At present, gallbladder cancer mostly adopts the FAM regimen (fluorouracil 1.0g, doxorubicin 40mg, mitomycin 20mg) and the FMP regimen (fluorouracil 1.0g, mitomycin 10mg, carboplatin 500mg). A multicenter randomized clinical study using the FAM regimen abroad showed that for patients with gallbladder cancer who have lost the opportunity for surgery, chemotherapy can significantly reduce the tumor volume, prolong the survival period, and even completely relieve a small number of cases. Selective arterial catheterization and infusion of chemotherapy drugs can reduce systemic toxic reactions. Generally, during surgery, a catheter is placed from the right gastroepiploic artery into the hepatic artery, and a drug pump is buried subcutaneously. After the incision heals, the FMP regimen is selected and repeated every 4 weeks according to the condition. In addition, iodized oil (with chemotherapy drugs added) is injected through the portal vein so that its particles can fully enter the liver sinusoids, which can play a role in local chemotherapy and temporarily block the tumor spread pathway. The clinical application has achieved certain results and provided a feasible treatment approach for patients with unresectable gallbladder cancer and liver metastasis. Intraperitoneal infusion of cisplatin and 5-FU has a certain effect on the prevention and treatment of peritoneal implantation and metastasis of gallbladder cancer. At present, research on combined chemotherapy of 5-FU, levamisole and folic acid is underway, and good results are expected.

(3) Other treatments: including interventional therapy, immunotherapy, etc., although it is difficult to achieve the treatment goal, it may improve the patient's condition, relieve pain, and prolong survival time. If advanced gallbladder cancer invades the liver parenchyma extensively from the gallbladder bed, or invades one hepatic duct from the gallbladder neck, or even multiple metastases occur in one liver, interventional therapy can be used, often through hepatic artery catheterization for embolization and chemotherapy, which can achieve better results.

Recent studies have found that K-ras, c-erbB-2, c-myc, p53, p15, p16 and nm23 genes are closely related to the occurrence, development and outcome of gallbladder cancer. Immunotherapy and the application of various biological response modifiers such as interferon, interleukin, etc. are often combined with radiotherapy and chemotherapy to improve their efficacy. In addition, thermotherapy is still in the exploratory stage and needs further research.

Given the current poor efficacy of gallbladder cancer treatment, it is reasonable to actively explore various comprehensive treatment measures, which are expected to alleviate patients' symptoms and improve prognosis.

Gallbladder cancer treatment with traditional Chinese medicine

There is currently no treatment for this disease.

Prognosis

The prognosis of gallbladder cancer is very poor, with the overall 5-year survival rate less than 5%. It is mainly related to the high degree of malignancy of the tumor, early metastasis and spread, and low early diagnosis and surgical resection rate. As mentioned above, the effect of tumor treatment is closely related to the stage of gallbladder cancer. Patients with stage I and II gallbladder cancer accidentally discovered after cholecystectomy according to benign gallbladder disease often survive for a long time. It is reported that the 5-year survival rate can reach 64% to 86%; on the contrary, the prognosis of cases above stage III is very poor. If the tumor has invaded the entire gallbladder layer, almost all deaths within 2.5 years after the operation.

Since the prognosis of early gallbladder cancer is significantly better than those who develop lymph node metastasis, striving to improve the detection rate of asymptomatic early gallbladder cancer has become a hot topic in recent years. Judging from the current domestic and foreign research situation, to promptly detect early gallbladder cancer, it can only be surgical treatment for benign bile tract diseases. By treating precancerous diseases and high-risk factors of gallbladder cancer, the treatment level of gallbladder cancer can be improved.

Dietary therapy for gallbladder cancer

(1) Radish and water chestnut porridge: Cut 30 grams of radish and water chestnuts into shreds, add 100 grams of rice, and cook porridge and eat.

(2) Coix seed porridge: 50 grams of coix seed, 100-150 grams of rice, add water to cook porridge and eat.

Dietary therapy for metastasis of gallbladder cancer

(1) Ginseng and maize porridge: 3 grams of American ginseng and 10 grams of Ophiopogon japonicus, chop them all up, add 100 grams of rice, cook the porridge together, and eat for breakfast.

(2) Ginseng and Qi Porridge: 10 grams of Prince Ginseng, 10 grams of wolfberry, 10 grams of Astragalus, 50-100 grams of rice, cook porridge together and eat for breakfast or snacks.

1 Avoid eating greasy foods;

2 Avoid eating stimulating drinks;

3 Avoid eating spicy and irritating foods.