[有片]膽囊在人體內有什麼用?

An underestimated digestive organ

In the long history of human medical exploration,gallbladderThe liver has always played a subtle and contradictory role. This pear-shaped sac-like organ, located below the liver, is only 8-12 centimeters long and has a capacity of about 50 milliliters, yet it plays a crucial role in the digestive system. Ancient Egyptians recorded the anatomical structure of the liver and gallbladder in the Ebers Papyrus dating back to 2000 BC, and believed that bile was closely related to human emotions and health. Hippocrates, in his "four humors" theory proposed in the 4th century BC, further considered "black bile" as one of the important humors influencing human character and health.

Today, our understanding of the gallbladder far surpasses that of our ancestors, yet the importance of this organ is often underestimated. The incidence of gallbladder disease in modern people has risen significantly. According to data from the World Health Organization in 2022, approximately 101-201% of adults worldwide suffer from gallstones, a considerable portion of whom require medical intervention.

Anatomical structure and physiological function of the gallbladder

The gallbladder is a thin-walled sac-like organ located in the gallbladder fossa on the visceral surface of the liver, below the right costal margin. It is formed by the cystic duct and the common hepatic duct. Its anatomical structure can be divided into three parts: the base, the body, and the neck. The gallbladder base is rounded and rich in elastic fibers, usually protruding from the lower border of the liver. The gallbladder body is the main storage site and contains abundant smooth muscle. The gallbladder neck gradually tapers and continues into the cystic duct, which contains a spiral Heister valve to prevent excessive expansion or torsion.

The gallbladder has the functions of concentrating and storing energy.bileBile dissolves fats and alcohol. The liver continuously secretes bile, which is stored in the gallbladder and released into the digestive tract to aid in fat digestion when needed. The common hepatic duct descending from the liver merges with the cystic duct to form the common bile duct, which passes through the pancreas.Hepatopancreatic ampullaBile andpancreatic juiceMix, side by sideDuodenum.

The gallbladder is primarily controlled by neurohormones.Cholecystokinin(CCK) causes the gallbladder to contract, releasing bile into the bile ducts. Other hormones, on the other hand, cause the gallbladder to relax in order to store bile.

From a histological perspective, the gallbladder wall is divided into three layers from the inside out: the mucosa, the muscularis propria, and the adventitia. The mucosa forms high, branching folds, and its epithelium consists of a single layer of columnar cells with strong absorptive function. The muscularis propria is composed of longitudinal and oblique smooth muscle fibers, which promote bile expulsion upon contraction. The adventitia is mostly serosa, with only a small portion of connective tissue connecting it to the liver. The core function of the gallbladder is to store, concentrate, and release bile continuously secreted by the liver.

An adult liver secretes approximately 600-1000 ml of bile daily, which is transported to the gallbladder via the hepatic ducts. The gallbladder mucosa actively absorbs water and electrolytes, concentrating the bile 5-10 times for later use. After eating, especially when fatty foods are ingested, the small intestinal mucosa secretes cholecystokinin (CCK), stimulating gallbladder contraction and relaxation of the sphincter of Oddi, allowing concentrated bile to flow into the duodenum to assist in the emulsification and digestion of fats.

Bile storage

The liver is the site of bile production, continuously secreting approximately 600-800 ml of bile daily. During non-digestive periods, when the body is not eating, most of the bile secreted by the liver enters the gallbladder through the hepatic ducts and cystic ducts for storage. The gallbladder acts like a "small warehouse," effectively collecting and storing bile, preventing it from continuously flowing into the intestines and causing waste, while also ensuring that enough bile is available when food needs to be digested. The normal gallbladder capacity is generally 40-60 ml, but it has a certain degree of elasticity and can expand appropriately to accommodate more bile. For example, after prolonged fasting or a low-fat diet, the gallbladder will gradually fill and expand, and its capacity may exceed the normal range.

The gallbladder's function of storing bile is crucial for maintaining normal digestive cycles. While eating is typically intermittent, bile secretion from the liver is continuous. Without the gallbladder's storage function, excess bile flowing into the intestines during non-digestive periods not only fails to fulfill its digestive role but may also irritate the intestinal mucosa. The gallbladder allows bile to be released in a concentrated manner when needed, improving digestive efficiency. Studies have shown that patients who have undergone gallbladder removal, lacking a bile storage organ, may experience fat malabsorption, leading to symptoms such as bloating and diarrhea, impacting their quality of life.

Concentrated bile

The gallbladder mucosa has a strong ability to absorb water and electrolytes, a characteristic that allows bile to be concentrated within the gallbladder. Freshly produced bile, secreted from the liver, has a high water content and is relatively dilute. Once in the gallbladder, the gallbladder mucosa absorbs most of the water and some electrolytes back into the body through active transport and passive diffusion, increasing the concentration of effective components such as bile salts, bile pigments, and cholesterol, thus concentrating the bile. Generally, bile can be concentrated 5-10 times in the gallbladder. For example, the concentration of bile salts in freshly secreted bile from the liver may be 2-3 g/L, but after gallbladder concentration, the concentration can increase to 10-20 g/L.

Concentrated bile has significantly enhanced digestive capacity. Bile salts are important components of bile involved in fat digestion and absorption. Increased concentration allows bile salts to more effectively emulsify fat particles during digestion, breaking down large fat droplets into smaller fat microparticles, increasing the contact area between fat and lipases, and promoting fat breakdown and absorption. Furthermore, concentrated bile also facilitates the absorption of fat-soluble vitamins (such as vitamins A, D, E, and K). If gallbladder function is impaired and bile cannot be concentrated properly, even if the liver secretes a normal amount of bile, insufficient concentration of effective components in the bile may lead to impaired fat digestion and absorption, potentially causing symptoms such as aversion to fatty foods and steatorrhea.

Excretion of bile

Eating is the primary factor stimulating gallbladder contraction, especially after consuming high-fat foods. The body stimulates gallbladder contraction through both neural and humoral pathways, promoting bile excretion. Neurally, the act of eating and the stimulation of the stomach and small intestine by food can trigger a vagus nerve reflex, causing gallbladder contraction and relaxation of the sphincter of Oddi, allowing bile to drain from the gallbladder into the common bile duct and then into the duodenum. Humorally, when the digestive products of fats and proteins enter the small intestine, they stimulate the intestinal mucosa to release cholecystokinin (CCK). CCK, circulating in the bloodstream, acts on the gallbladder smooth muscle and the sphincter of Oddi, causing strong gallbladder contraction and relaxation of the sphincter of Oddi, resulting in a large amount of bile being released into the intestines.

The process of bile excretion is crucial for the digestion and absorption of fats. Bile salts in bile emulsify fats, breaking them down into tiny particles that facilitate the action of lipases, thus promoting fat digestion. Simultaneously, bile salts can form water-soluble complexes with fat breakdown products, further promoting fat absorption. Furthermore, components in bile, such as bile pigments, participate in some metabolic processes in the intestines. If the gallbladder's bile excretion function is abnormal, such as in cases of cystic duct obstruction or sphincter spasm of the bile duct, bile discharge can be impaired, leading to increased pressure within the gallbladder and causing conditions like cholecystitis and biliary colic. Clinically, some patients experience right upper quadrant pain after consuming high-fat meals, which may be due to impaired bile excretion function of the gallbladder.

secretory function

The epithelial cells of the gallbladder mucosa have a secretory function, secreting approximately 20 ml of viscous substance daily, mainly composed of mucin. This mucin forms a protective mucus layer covering the surface of the gallbladder mucosa. This mucus layer plays several important roles: First, it protects the gallbladder mucosa from the erosion and dissolution of bile, as bile salts and other components in bile are irritating and could damage the mucosal cells if they come into direct contact with the gallbladder mucosa. Second, the mucus layer acts as a lubricant, reducing friction on the mucosa as bile flows through the gallbladder and protecting its integrity. Furthermore, this mucus layer prevents bacteria and other harmful substances from adhering to the surface of the gallbladder mucosa, reducing the risk of gallbladder infection.

The mucus secreted by the gallbladder mucosa also plays a role in the development and progression of gallbladder diseases. When the gallbladder is inflamed, the secretory function of the mucosa may be affected, with the amount of mucus secreted increasing or decreasing, and the composition of the mucus also changing. For example, in patients with cholecystitis, the mucus secreted by the gallbladder mucosa may contain more inflammatory cells and proteins, and these changes may further affect gallbladder function and exacerbate the inflammatory response. In addition, certain gallbladder diseases, such as gallbladder polyps and gallbladder cancer, may also be associated with abnormal gallbladder mucosal secretory function and changes in mucus composition, but the specific mechanisms require further investigation.

Regulating biliary pressure

The gallbladder acts as a flexible buffer within the biliary system, playing a crucial role in regulating biliary pressure. The biliary system is a continuous network of ducts, including intrahepatic bile ducts, extrahepatic bile ducts, the gallbladder, and the common bile duct, through which bile flows. When the liver increases bile secretion, or when obstruction occurs in the lower segment of the bile duct (such as due to gallstones, tumors, or other causes leading to common bile duct stenosis), the pressure within the bile duct rises. In this situation, the gallbladder can expand by dilating to accommodate some bile, thereby relieving pressure within the bile duct and preventing damage to the liver and bile ducts from excessively high pressure. Conversely, when fasting or when biliary pressure decreases, the gallbladder can contract to release stored bile into the bile duct as needed, maintaining a relatively stable pressure within the bile duct.

The gallbladder's function of regulating biliary pressure is crucial for maintaining the normal physiological function of the biliary system. After gallbladder removal, the buffering effect of the gallbladder is lost, affecting the pressure regulation mechanism of the biliary system and potentially increasing pressure fluctuations within the bile ducts. Long-term abnormal biliary pressure can lead to adverse consequences such as bile duct dilatation, cholangitis, and bile duct stone formation. Studies have shown that patients who have undergone cholecystectomy have a relatively higher risk of developing bile duct stones, which may be related to the imbalance in biliary pressure regulation after gallbladder removal. Therefore, protecting the normal function of the gallbladder is of great importance for maintaining the health of the biliary system.

Immune function

Recent studies have found that the gallbladder also plays a role in the human immune system. The gallbladder mucosa secretes immune substances such as immunoglobulin A (IgA). IgA is an important secretory antibody that can form an immune defense on the surface of the gallbladder mucosa, recognizing and binding to pathogens such as bacteria and viruses entering the bile duct, preventing them from adhering to the gallbladder mucosa and invading body tissues, thus playing a role in local immune defense. In addition, the gallbladder wall contains abundant lymphoid tissue, which is part of the body's immune system and can participate in immune responses. When pathogens invade the bile duct, the lymphoid tissue of the gallbladder wall can be activated, producing immune cells such as lymphocytes and macrophages. These immune cells can engulf and eliminate pathogens, maintaining the health of the biliary system.

The immune function of the gallbladder plays a crucial role in the development of certain gallbladder diseases. For example, bacterial infection is a common cause of cholecystitis. Under normal circumstances, the gallbladder's immune function effectively resists bacterial invasion. However, when this immune function is impaired, such as due to long-term alcohol abuse, malnutrition, or certain immune system diseases, bacteria can more easily breach the immune defenses, multiply within the gallbladder, and cause an inflammatory response. Furthermore, the development of gallbladder cancer may also be related to abnormal gallbladder immune function. Decreased immune function may weaken the body's ability to monitor and eliminate cancer cells, thereby increasing the risk of gallbladder cancer. Therefore, maintaining normal gallbladder immune function plays a positive role in preventing gallbladder diseases.

In addition, the gallbladder plays an important endocrine role. Gallbladder epithelial cells secrete various bioactive substances, such as prostaglandins, mucins, and electrolytes, regulating the gallbladder's own absorption and secretion processes. Recent studies have also found that the gallbladder may participate in metabolic regulation through the gut-hepatic axis and is associated with metabolic diseases such as insulin resistance and non-alcoholic fatty liver disease.

Historical Evolution of Gallbladder Diseases

Historical records of gallbladder disease date back to ancient civilizations. The earliest known case of gallstones was found in ancient Egyptian mummies—multiple cholesterol stones were discovered in the body of a priestess from around 1500 BC. Hippocrates warned, "When severe abdominal pain is accompanied by jaundice, it is an ominous sign," likely describing the serious consequences of common bile duct obstruction caused by stones.

During the Middle Ages, gallbladder disease was widely believed to be associated with a "melancholy temperament," and treatments were largely based on humoral theory, including bloodletting, purging, and herbal remedies. During the Renaissance, with the development of anatomy, people's understanding of the gallbladder gradually became more scientific. In the 16th century, the anatomist Vesalius described the morphology of the gallbladder and its relationship with surrounding organs in detail in his book *De humani corporis fabrica*.

Significant progress was made in the diagnosis and treatment of gallbladder diseases in the 18th and 19th centuries. In 1882, German surgeon Carl Langenbuch successfully performed the first elective cholecystectomy, ushering in a new era for biliary surgery. However, the high postoperative mortality rate (20-30%) limited its widespread application.

The 20th century witnessed revolutionary advancements in the diagnosis and treatment of gallbladder diseases. The invention of oral cholecystography in 1924 made the diagnosis of gallstones possible; the application of ultrasound technology in the 1950s further improved diagnostic accuracy; and in 1985, French physician Mouret performed the first laparoscopic cholecystectomy, greatly reducing surgical trauma and recovery time, and becoming the gold standard for gallbladder surgery.

In the 21st century, with changes in lifestyle and population aging, the epidemiological characteristics of gallbladder disease have undergone significant changes. The widespread adoption of high-fat, high-calorie diets has led to a significant increase in the incidence of cholesterol gallstones; increased life expectancy has increased the elderly patient population; and factors such as metabolic syndrome and rapid weight loss have also become new risk factors.

Gallstones: Formation Mechanisms and Global Trends

Gallstones are one of the most common digestive system diseases in the world. Based on their chemical composition, they can be divided into three main categories: cholesterol stones, pigment stones, and mixed stones. Cholesterol stones account for more than 75% of gallstone cases in Western countries, while pigment stones are more common in Asia.

Gallstone formation is a complex, multifactorial process, primarily involving three mechanisms: bile composition imbalance, gallbladder dysfunction, and nucleating factors. Cholesterol supersaturation is a prerequisite for cholesterol stone formation—when the cholesterol concentration in bile exceeds the solubility of bile salts and phospholipids, crystals precipitate. Reduced gallbladder motility leads to bile stasis, providing time and space for crystal aggregation and growth. Nucleating factors such as mucin glycoproteins accelerate the formation and aggregation of cholesterol monohydrate crystals.

Globally, the prevalence of gallstones varies significantly by region. North America and Europe have the highest prevalence, ranging from 101 TP3T to 201 TP3T; Asian countries have a relatively lower prevalence, around 31 TP3T to 101 TP3T, but this has increased rapidly in recent decades due to the Westernization of diets; Africa has the lowest prevalence, less than 51 TP3T. This difference is mainly related to genetic background, dietary structure, and environmental factors.

Global prevalence of gallstones (2023 data)

area	Prevalence (%)	Main types of stones	Key risk factors
North America	15-20	cholesterol stones	Obesity, metabolic syndrome
Europe	10-18	cholesterol stones	Age, female hormones
East Asia	5-10	Mixed/pigmented stones	Rapid weight loss, liver disease
South Asia	3-8	Pigment stones	Hemolytic diseases, infections
Africa	2-5	Pigment stones	Parasitic infection, malnutrition

Age is an independent risk factor for gallstone formation, with the prevalence increasing significantly with age after age 40. Significant gender differences are also observed—women are approximately 2-3 times more likely to develop gallstones than men, which is related to estrogen promoting hepatic cholesterol secretion and progesterone inhibiting gallbladder contraction. Pregnancy, multiple births, oral contraceptives, and hormone replacement therapy further increase the risk in women.

Other important risk factors include obesity (especially central obesity), rapid weight loss (such as after bariatric surgery), metabolic syndrome, diabetes, intestinal diseases (such as Crohn's disease), prolonged fasting, and total parenteral nutrition. Genetic factors also play an important role; those with a family history of gallstones have a 2-4 times increased risk.

Cholecystitis: The Pathological Process from Acute to Chronic

Cholecystitis is the most common inflammatory disease of the gallbladder, and it can be divided into two main categories based on its clinical course: acute and chronic. In acute cholecystitis, 90%-95% is caused by obstruction of the cystic duct by gallstones, while the remaining 5%-10% is acalculous cholecystitis, which is commonly seen in patients with severe trauma, major surgery, sepsis, or total parenteral nutrition.

The pathological process of acute cholecystitis with gallstones begins with obstruction of the cystic duct. Stone impaction leads to increased pressure within the gallbladder, obstructing blood flow to the gallbladder wall and triggering ischemia and inflammation. Cytotoxic substances produced by bile concentration (such as lysophosphatidylcholine) further damage the mucosal barrier, allowing for secondary bacterial infection (commonly Escherichia coli, Klebsiella pneumoniae, and Enterococci). The release of inflammatory mediators results in typical clinical manifestations: severe right upper quadrant pain, tenderness, fever, and elevated white blood cell count.

If acute inflammation recurs repeatedly or persists, it can progress to chronic cholecystitis. It is characterized by thickened fibrosis of the gallbladder wall, muscle atrophy, flattening of the mucosa, and chronic inflammatory cell infiltration. Gallbladder function gradually deteriorates, its contractile ability decreases, and it may eventually lose function completely (gallbladder dysfunction).

Although less common, acalculous cholecystitis is often more severe and frequently occurs in critically ill patients. Its pathogenesis is mainly related to cholestasis, gallbladder ischemia, and endotoxemia. Due to atypical clinical presentations and the fact that patients often have other serious underlying conditions, diagnosis and treatment are frequently delayed, leading to a higher risk of complications such as perforation and gangrene.

In terms of time, the natural history of cholecystitis typically goes through the following stages:

Asymptomatic gallstone stage (may last for several years)
Biliary colic attack (intermittent obstruction)
Acute cholecystitis (persistent obstruction and inflammation)
Complications (gangrene, perforation, abscess formation)
Chronic cholecystitis (fibrosis following repeated inflammation)

Complications are a leading cause of death from cholecystitis, including:

Gangrene and perforation of the gallbladder (occurring in acute cases of 5%-10%)
Pericholecystic abscess
A choledochoenterostomy (stones passing through a fistula into the intestines may cause intestinal obstruction)
Gallstone-induced intestinal obstruction (gallstone lodged in the terminal ileum)
Gallbladder cancer (a rare but serious consequence of long-term chronic inflammation)

Gallbladder and Overall Health: Effects Beyond Digestion

Traditional views regard the gallbladder as a simple digestive aid, but mounting evidence suggests that it is closely related to the health of multiple systems throughout the body.

Metabolic regulation
The gallbladder influences systemic metabolism through its role in the bile acid cycle. Bile acids are not only digestive agents but also important signaling molecules that regulate glucose, lipid, and energy metabolism by activating farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). After gallbladder removal, the bile acid cycle pattern changes, and fasting and postprandial bile acid levels fluctuate abnormally, potentially having long-term metabolic effects.

Multiple large-scale studies have shown that cholecystectomy is associated with an increased risk of metabolic syndrome. A 10-year cohort study found that patients who underwent cholecystectomy had a 23% higher risk of developing insulin resistance and type 2 diabetes than controls. Possible mechanisms include altered bile acid pool composition, impaired FXR signaling pathway, and changes in intestinal hormone secretion patterns.

Influence of gut microbiota
The gallbladder, as a reservoir of bile acids, periodically releases high concentrations of bile acids into the intestines, regulating the gut microbiota. Bile acids have antibacterial properties, inhibiting the overgrowth of certain pathogens while promoting the colonization of beneficial bacteria. After gallbladder removal, bile acids continue to flow slowly into the intestines, losing this periodic flushing effect, which may lead to small intestinal bacterial overgrowth (SIBO) and gut microbiota dysbiosis.

Studies have found that patients who have undergone cholecystectomy have reduced gut microbiota diversity, altered Bacteroidetes/Firmwallis ratios, and a slightly increased risk of inflammatory bowel disease. These changes may further affect liver and overall health through the gut-liver axis.

Association with non-alcoholic fatty liver disease (NAFLD)
Gallbladder disease and NAFLD often coexist and influence each other. On the one hand, abnormal cholesterol metabolism in NAFLD patients leads to increased bile saturation, promoting gallstone formation; on the other hand, abnormal gallbladder function may exacerbate hepatic steatosis and inflammation by altering bile acid signaling.

Interestingly, "gallbladder wall thickening," a common finding on ultrasound examinations, may be an early marker of NAFLD, even preceding elevated liver enzymes. This suggests that changes in gallbladder morphology may reflect the liver's metabolic state and have potential early warning value.

Long-term effects of cholecystectomy
Cholecystectomy is the gold standard for treating symptomatic gallstones, with over 2 million procedures performed globally each year. While most patients experience improved quality of life after surgery, some may experience long-term complications.

Biliary diarrhea: Approximately 5%-10% patients experience secretory diarrhea due to increased concentrations of bile acids in the colon.
Sphincter dysfunction: May cause abdominal pain similar to biliary colic.
Symptoms of esophageal reflux: Some studies show a slightly increased risk.
Colorectal cancer risk: Controversial, some studies suggest a slight increased risk of right-sided colorectal cancer.
Metabolic changes: As mentioned earlier, this may increase the risk of insulin resistance.

It is worth noting that most of these increased risks are small and are offset by the benefits of symptom relief and reduced risk of acute complications. Individualized assessment remains the basis for clinical decision-making.

The Evolution of Diagnostic Technologies: From Palpation to Molecular Imaging

The diagnostic methods for gallbladder diseases have undergone a leap forward from relying solely on physical signs to modern multimodal imaging.

Traditional physical diagnosis
In the late 19th and early 20th centuries, physicians primarily relied on detailed medical histories and skilled physical examinations to diagnose gallbladder diseases. Murphy's sign (right upper quadrant tenderness during deep inspiration leading to cessation of inspiration), described by Chicago surgeon John Benjamin Murphy in 1903, remains an important clinical marker of acute cholecystitis. Other classic signs include: referred pain in the right subscapular region (Boas's sign), right upper quadrant muscle guarding, and a palpable enlarged gallbladder.

Advances in Radiology
In 1924, American physicians Evarts Graham and Warren Cole developed oral cholecystography, achieving the first morphological visualization of the gallbladder. After the patient ingested an iodine-containing contrast agent, an X-ray was taken, revealing the filling defects caused by gallstones. This technique dominated gallbladder diagnosis for nearly 50 years until the advent of ultrasound in the 1970s.

Ultrasound examination has revolutionized gallbladder imaging. It boasts advantages such as being radiation-free, non-invasive, low-cost, and highly accurate. Its sensitivity and specificity for gallstones exceed those of 95%, making it the preferred initial screening method. Under ultrasound, gallstones appear as hyperechoic masses with acoustic shadowing, and can move with body position. Furthermore, it can assess gallbladder wall thickness, surrounding fluid, and the Murphy's sign.

Computed tomography (CT) has relatively low sensitivity for detecting gallstones (approximately 801 TP3T), but it is more valuable for assessing complications such as perforation and abscess. Magnetic resonance cholangiopancreatography (MRCP), on the other hand, can non-invasively visualize the entire biliary tree and is particularly valuable for suspected common bile duct stones.

Functional imaging technology
For patients suspected of gallbladder dysfunction, gallbladder emptying fraction (GBEF) measurement is of significant value. The most commonly used method is cholecystokinin-stimulated biliary scintillation: after intravenous injection of a CCK analog, a gamma camera is used to track the excretion of the radiolabeled bile acid analog and calculate the gallbladder emptying rate. A GBEF below 35 %-40 % is considered abnormal, suggesting impaired gallbladder motility.

Emerging technologies
In recent years, new technologies such as endoscopic ultrasound (EUS) and transoral cholangioscopy have further improved diagnostic accuracy. EUS is particularly sensitive to the detection of microlithiasis and biliary sludge, and can also perform interventional treatments simultaneously with diagnosis. Molecular imaging techniques, such as PET tracers targeting bile acid transporters, are under development and are expected to enable visualization at the functional and molecular levels.

The Evolution of Treatment Strategies: From Conservative Treatment to the Minimally Invasive Revolution

Treatment strategies for gallbladder diseases are constantly evolving as our understanding of the disease deepens and technology advances.

Medical treatment
Asymptomatic gallstones generally do not require treatment, only regular observation and lifestyle adjustments. For symptomatic patients who are unwilling or unsuitable for surgery, oral bile acid litholytic therapy (such as ursodeoxycholic acid) can be considered. This method is suitable for cholesterol stones <1.5cm in diameter and those with normal gallbladder function, but the efficacy is limited (complete dissolution rate is approximately 50% for %), the treatment duration is long (6-24 months), and the recurrence rate after discontinuation of medication is high (50% recurrence within 5 years for 50% %).

Initial treatment for acute cholecystitis includes fasting, intravenous fluids, pain relief, and antibiotics. However, medical treatment alone cannot resolve the underlying obstruction and carries a high risk of recurrence; it is usually used as a transitional measure before surgery.

The evolution of surgical treatment
Open cholecystectomy (OC) has been continuously improved throughout the first half of the 20th century since its first performance in 1882. By the 1970s, the mortality rate of elective OC had dropped to <0.51 TP3T, making it a safe and effective standard procedure. However, open surgery requires a larger incision, results in significant postoperative pain, and has a long recovery time (4-6 weeks).

In 1985, French surgeon Philippe Mouret performed the first laparoscopic cholecystectomy (LC), ushering in a new era of minimally invasive surgery. LC requires only 3-4 small incisions of 0.5-1 cm, resulting in less postoperative pain, faster recovery (1-2 weeks), and aesthetically pleasing scars, quickly becoming the standard treatment for symptomatic gallstones. By 2000, LC accounted for over 90% of all cholecystectomies.

Challenges and Progress in the Laparoscopic Era
The widespread adoption of LC (lower biliary tract intubation) has also brought new challenges, the most serious being a slightly increased incidence of bile duct injury (BDI) compared to the OC (occlusive duct intubation) period (0.3%-0.6% vs 0.1%-0.2%). To improve safety, several technical improvements have been introduced:

Critical View of Safety (CVS): Requires clear exposure of the confluence of the cystic duct and common bile duct.
Intraoperative cholangiography: selectively used for the identification of anatomical variations.
Fluorescence biliary imaging: Intraoperative intravenous injection of indocyanine green, visualization of biliary structures under near-infrared light.

For complex cases where LC is not suitable (such as severe inflammation, cirrhosis, portal hypertension), some centers use percutaneous cholecystostomy as a temporary measure, or perform laparoscopic-assisted small incision surgery (mini-laparotomy).

Integration of day surgery and ERCP
With advancements in anesthesia and perioperative management, LC with approximately 70%-80% can now be performed as a day surgery, allowing patients to be discharged 6-8 hours post-surgery, thus reducing costs and increasing efficiency.

For patients with concomitant common bile duct stones, the integrated treatment of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic cholecystoscopic surgery (LC) has become the standard approach. The procedure typically employs either "preoperative ERCP + LC" or "LC with intraoperative ERCP," with the choice made individually based on stone size, local technology, and available resources.

Future directions: Gallbladder-preserving stone removal and natural orifice surgery
As awareness of the importance of gallbladder function deepens, some centers are exploring selective gallbladder-preserving stone removal surgery, particularly for young patients with a single gallstone and good gallbladder function. Long-term efficacy still requires further research to confirm.

New technologies such as Natural Orifice Transluminal Endoscopic Surgery (NOTES) and robot-assisted surgery are being explored, promising to further reduce trauma. However, these technologies are currently expensive, and their advantages require more evidence to support their claims.

Gallbladder Cancer: The Silent Killer and Prevention Strategies

Although gallbladder cancer is relatively rare (accounting for 0.51-1.51% of all gastrointestinal tumors), its prognosis is extremely poor, with a 5-year survival rate of <101%, mainly due to its insidious early symptoms and rapid progression. Most gallbladder cancers are associated with gallstones and chronic inflammation; approximately 85% of cases are associated with gallstones, but only 11-31% of gallstone patients develop cancer.

Risk factors and carcinogenesis pathways
Key risk factors include: gallstones (especially those >3cm, which increase the risk by 10 times), gallbladder calcification ("porcelain gallbladder" has a high risk of malignant transformation, up to 25%), gallbladder polyps (>1cm or those growing rapidly have a high risk), congenital bile duct abnormalities (such as pancreaticobiliary maljunction), typhoid carrier status (increases the risk by 8 times), and exposure to certain industrial chemicals.

The carcinogenesis process typically follows a multi-stage pattern of "inflammation-metaplasia-dysplasia-carcinoma". Chronic inflammation leads to repeated damage and repair of the epithelium, triggering intestinal metaplasia and dysplasia, eventually accumulating enough gene mutations to cause malignant transformation. Common molecular alterations include: TP53 mutation (50%-70%), CDKN2A/p16 inactivation (45%), KRAS mutation (10%-15%), and HER2/neu amplification (10%-15%).

Diagnostic and Treatment Challenges
Early-stage gallbladder cancer is often asymptomatic or presents only with nonspecific dyspepsia, making it difficult to detect early. In advanced stages, symptoms may include right upper quadrant pain, weight loss, jaundice, or a palpable mass. Ultrasound and CT are the primary imaging methods, but their sensitivity for early lesions is limited.

Incidental discovery (found pathologically after cholecystectomy for benign disease) accounts for the majority of curable cases. For T1a stage cancer confined to the mucosa or muscle layer, simple cholecystectomy may be curative; however, those with deeper infiltration require extended resection including part of the liver and lymph node dissection. Patients with advanced stage cancer have a very poor prognosis, and chemotherapy and radiotherapy have limited effectiveness.

Prevention strategies
Given the poor efficacy of treatment, prevention becomes crucial. Strategies include:

Patients with symptomatic gallstones should undergo cholecystectomy in a timely manner.
Asymptomatic but high-risk gallstones (>3cm, porcelain gallbladder, polyps >1cm) should be considered for prophylactic removal.
Thorough treatment of typhoid carriers
Regular ultrasound screening for high-risk groups (such as patients with pancreaticobiliary malformation).

Gallbladder Health Maintenance and Future Outlook

Maintaining gallbladder health requires a comprehensive strategy, involving lifestyle adjustments, risk factor management, and appropriate screening.

Diet and Nutrition
Dietary factors play a central role in gallstone formation. Prevention strategies include:

Maintain a healthy weight, avoiding obesity but also avoiding rapid weight loss (>1.5kg/week).
Limit intake of refined carbohydrates and saturated fats
Increase dietary fiber (especially soluble fiber) and plant protein.
Eat regularly and avoid prolonged fasting.
Moderate coffee consumption may reduce the risk (3-4 cups/day).
Nut intake is associated with a reduced risk (possibly by improving insulin sensitivity).

Drug prevention
For high-risk groups (such as those undergoing rapid weight loss), medication may be beneficial for prevention. Ursodeoxycholic acid (UDCA) 10 mg/kg/day can effectively prevent stone formation after bariatric surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may also reduce stone formation by inhibiting prostaglandin synthesis.

Sports and Lifestyle
Regular physical activity can enhance gallbladder contraction and reduce bile stasis. Studies have shown that at least 2-3 hours of moderate-intensity exercise per week can reduce the risk of symptomatic gallstones. Avoiding prolonged sitting and quitting smoking also help reduce the risk.

Future research directions
The field of gallbladder research still holds many unsolved mysteries and opportunities for innovation:

Gallbladder organ-on-a-chip model: used to study bile composition and gallstone formation mechanisms.
Targeted drugs: such as bile acid transport inhibitors and nucleation factor antagonists
Gene therapy: targeting hereditary cholesterol metabolism disorders
Artificial intelligence-assisted diagnosis: Improving ultrasound's ability to identify early-stage gallbladder cancer.
Gallbladder organoids: used for disease modeling and drug screening
Microbiome regulation: Influencing bile acid metabolism through probiotics/prebiotics

Global burden of gallbladder disease over time (1990-2030 projections)

years	Incidence of gallbladder disease (per 100,000 people)	Laparoscopic surgery ratio (%)	Open abdominal surgery ratio (%)
1990	120	15	80
2000	130	30	70
2010	140	65	30
2020	150	85	12
2030	160	92	5

Data Analysis and Observation

Incidence trendThe incidence of gallbladder disease is expected to increase steadily from 1990 to 2030, from 120 cases per 100,000 people to 160 cases per 100,000 people.
Changes in treatment methods:

The proportion of laparoscopic surgeries has increased significantly, rising from 151 TP3T in 1990 to 921 TP3T in 2030.
The proportion of open surgeries has decreased significantly, from 801 TP3T in 1990 to only 51 TP3T in 2030.
2010 was a significant turning point, with the proportion of laparoscopic surgeries (651 TP3T) exceeding that of open surgeries (301 TP3T) for the first time.

As the chart shows, although the incidence of gallbladder disease continues to rise, the treatment method has almost completely transitioned from traditional open surgery to laparoscopic minimally invasive surgery, reflecting the improvement of the patient's treatment experience due to technological advancements.

in conclusion

The gallbladder, once considered by Hippocrates to be an organ that influences human nature, has undergone a process of understanding from mystery to clarity in the course of thousands of years of medical development. From the ancient reverence for bile to the humoral theory of the Middle Ages, and then to modern molecular medicine, our understanding of this small organ has continued to deepen.

The gallbladder is no longer viewed as a simple bile storage bag, but as a complex, active organ involved in digestion, metabolic regulation, and gut microbiota balance. The global burden of gallbladder disease continues to increase, closely related to modern lifestyles and an aging population. Advances in diagnostic and treatment technologies, particularly the widespread adoption of laparoscopic surgery, have significantly improved patient outcomes.

However, challenges remain: early diagnosis of gallbladder cancer remains difficult; the long-term metabolic effects of cholecystectomy require further investigation; and uneven distribution of medical resources across different regions leads to significant differences in the quality of care. Future research needs to focus more on the systemic effects of the gallbladder and develop more effective prevention and treatment strategies.

In this era of precision medicine, we should re-examine the importance of the gallbladder, neither over-treating asymptomatic diseases nor neglecting its role in overall health. Through a scientific lifestyle, appropriate screening strategies, and individualized treatment choices, we can better maintain this small yet vital digestive organ and promote overall health.

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