Gallbladder cancer is a relatively uncommon

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, with an incidence of fewer than 2 cases per 100,000 people per year in the United States. It is particularly common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics. If it is diagnosed early enough, it can be cured by removing the

gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...

, part of the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

and associated

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

s. Most often it is found after

symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...

such as

abdominal The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the to ...

pain,

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

and vomiting occur, and it has spread to other

organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic keyboard instrument ** Hammond ...

s such as the liver. It is a rare cancer that is thought to be related to gallstones building up, which also can lead to

calcification Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature M ...

of the gallbladder, a condition known as

porcelain gallbladder Porcelain gallbladder is a calcification of the gallbladder believed to be brought on by excessive gallstones, although the exact cause is not clear. As with gallstone disease in general, this condition occurs predominantly in overweight female p ...

. Porcelain gallbladder is also rare. Some studies indicate that people with porcelain gallbladder have a high risk of developing gallbladder cancer, but other studies question this. The outlook is poor for recovery if the cancer is found after symptoms have started to occur, with a 5-year survival rate of close to 3%.

Signs and symptoms

* Steady pain in the upper right abdomen *

Indigestion Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...

* Dyspepsia (gas) *

Bilious Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile) ...

vomit *

Weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

Loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...

Weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...

Jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

due to obstruction Early symptoms mimic gallbladder inflammation due to gallstones. Later, the symptoms may be that of

biliary A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...

and stomach obstruction. Of note,

Courvoisier's law Courvoisier's law (known as Courvoisier's sign or Courvoisier–Terrier's sign, or Courvoisier syndrome) states that a painless palpably enlarged gallbladder accompanied with mild jaundice is unlikely to be caused by gallstones. Usually, the te ...

states that in the presence of a palpably enlarged gallbladder which is nontender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones. This implicates possible malignancy of the gallbladder or pancreas, and the swelling is unlikely due to gallstones due to the chronic inflammation associated with gallstones leading to a shrunken, non-distensible gallbladder. However, Ludwig Georg Courvoisier's original observations, published in Germany in 1890, were not originally cited as a law, and no mention of malignancy or pain (tenderness) was made. These points are commonly misquoted or confused in the medical literature.

Risk factors

* Gender— approximately twice as common in women than men, usually in seventh and eighth decades *

Obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

* Chronic

cholecystitis Cholecystitis is inflammation of the gallbladder. Symptoms include right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks (biliary colic) precede acute cholecystitis. The pai ...

and

cholelithiasis A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of mig ...

* Primary sclerosing cholangitis * Chronic

typhoid Typhoid fever, also known as typhoid, is a disease caused by ''Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several d ...

infection of gallbladder; chronic

Salmonella typhi ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of '' Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includi ...

carriers have 3 to 200 times higher risk of gallbladder cancer than non-carriers and 1–6% lifetime risk of development of cancer * Various single nucleotide polymorphisms (SNPs) have been shown to be associated with gallbladder cancer; however, existing genetic studies in GBC susceptibility have so far been insufficient to confirm any association * Gallbladder polyps * Calcified gallbladder wall (porcelain gallbladder) * Congenital abnormalities of the bile duct such as choledochal cyst

Diagnosis

Early diagnosis is not generally possible. People at high risk, such as women or Native Americans with gallstones, are evaluated closely. Transabdominal

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

, CT scan, endoscopic

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

, and MR cholangio-pancreatography (MRCP) can be used for diagnosis. A large number of gallbladder cancers are found incidentally in patients being evaluated for

, or gallstone formation, which is far more common. A biopsy is the only certain way to tell whether or not the tumorous growth is malignant. File:Gallbladder adenocarcinoma (3) lymphatic invasion histopathology.jpg, Gallbladder adenocarcinoma lymphatic invasion histopathology File:Gallbladder adenocarcinoma (1) histopathology.jpg, Incidentally discovered gallbladder cancer (

adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, o ...

) following a

cholecystectomy Cholecystectomy is the surgical removal of the gallbladder. Cholecystectomy is a common treatment of symptomatic gallstones and other gallbladder conditions. In 2011, cholecystectomy was the eighth most common operating room procedure performed i ...

. File:Gallbladder adenocarcinoma (2) histopathology.jpg, Gallbladder adenocarcinoma

histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Sp ...

Differential diagnosis

Xanthogranulomatous cholecystitis (XGC) is a rare form of

gallbladder disease Gallbladder diseases are diseases involving the gallbladder and is closely linked to biliary disease, with the most common cause being gallstones (cholelithiasis). The gallbladder is designed to aid in the digestion of fats by concentrating and ...

which mimics gallbladder cancer although it is not cancerous. It was first discovered and reported in the medical literature in 1976 by J.J. McCoy Jr., and colleagues.

Treatment

If detected early in a stage where it has not spread, gallbladder cancer can be treated by surgery. Surgery for gallbladder cancer is called radical

or extended cholecystectomy. It entails the removal of gallbladder along with adequate removal of its liver bed to the healthy tissue. The

lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

in the vicinity are also removed. Sometimes removal of a large part of the liver called hepatectomy is required to completely remove the tumor. The bile duct if involved also needs to be removed. However, with gallbladder cancer's extremely poor prognosis, most patients will die within a year of surgery. If surgery is not possible, endoscopic stenting or percutaneous transhepatic biliary drainage (PTBD) of the biliary tree can reduce jaundice and a stent in the stomach may relieve vomiting.

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

and

radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...

may also be used with surgery. If gallbladder cancer is diagnosed after cholecystectomy for stone disease (incidental cancer), re-operation to remove part of liver and lymph nodes is required in most cases. When it is done as early as possible, patients have the best chance of long-term survival and even cure.

Epidemiology

Most tumors are

s, with a small percent being

squamous cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

carcinomas. * Gallbladder cancer is relatively rare, affecting fewer than 5000 people in the United States per year * Gallbladder cancer is more common in South American countries, Japan, and Israel; in Chile, gallbladder cancer is the fourth most common cause of cancer deaths. * 5th most common gastrointestinal cancer * Up to 5 times more common in women than men depending on population (e.g. 73% female in China) * The age adjusted incidence rates of gallbladder cancer is highest in Chile, followed by in the state of Assam in India

Prognosis

The prognosis still remains poor. The cancer commonly spreads to the

, bile duct,

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

, and

duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...

Research

A better understanding of the biology of biliary tract cancers, including gallbladder cancer, is being achieved by advances in genomic profiling.Lamarca A, Barriuso J, McNamara MG, Valle JW. Biliary Tract Cancer: State of the Art and potential role of DNA Damage Repair. Cancer Treat Rev. 2018 Nov;70:168-177. doi: 10.1016/j.ctrv.2018.09.002. Epub 2018 Sep 8. PMID: 30218788 This research is providing insight into deficiencies in the tumor cell’s ability to accurately repair damages in their own DNA. The tumors in about 25% of patients with biliary tract cancer have some form of DNA damage repair deficiency. Knowledge of such deficiencies can be exploited to potentially increase response to treatment strategies that are currently available such as chemotherapy, radiotherapy or immunotherapy.

References

External links

U.S. National Cancer Institute Gallbladder Cancer Treatment (www.cancer.gov)
{{Authority control Digestive system neoplasia Gallbladder disorders Articles containing video clips Types of cancer