Gallbladder

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Gallbladder 

 

Gallbladder
The gallbladder sits beneath the liver.
Details
Precursor	Foregut
System	Digestive system
Artery	Cystic artery
Vein	Cystic vein
Nerve	Celiac ganglia, Vagus nerve
Identifiers
Latin	Vesica biliaris, vesica fellea
MeSH	D005704
TA	A05.8.02.001
FMA	7202

In vertebrates, the gallbladder 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 the structure and position of the gallbladder can vary significantly among animal species. It receives and stores bile, produced by the liver, via the common hepatic duct and releases it via the common bile duct into the duodenum, where the bile helps in the digestion of fats.

The gallbladder can be affected by gallstones, formed by material that cannot be dissolved – usually cholesterol or bilirubin, a product of haemoglobin breakdown. These may cause significant pain, particularly in the upper-right corner of the abdomen, and are often treated with removal of the gallbladder called a cholecystectomy (cholecyst means gallbladder). Cholecystitis, inflammation of the gallbladder, has a wide range of causes, including result from the impaction of gallstones, infection, and autoimmune disease.

Structure

The gallbladder is a hollow organ that sits in a shallow depression below the right lobe of the liver, that is grey-blue in life. In adults, the gallbladder measures approximately 7 to 10 centimetres (2.8 to 3.9 inches) in length and 4 centimetres (1.6 in) in diameter when fully distended. The gallbladder has a capacity of about 50 millilitres (1.8 imperial fluid ounces).

The gallbladder is shaped like a pear, with its tip opening into the cystic duct. The gallbladder is divided into three sections: the fundus, body, and neck. The fundus is the rounded base, angled so that it faces the abdominal wall. The body lies in a depression in the surface of the lower liver. The neck tapers and is continuous with the cystic duct, part of the biliary tree. The gallbladder fossa, against which the fundus and body of the gallbladder lie, is found beneath the junction of hepatic segments IVB and V.^[5] The cystic duct unites with the common hepatic duct to become the common bile duct. At the junction of the neck of the gallbladder and the cystic duct, there is an out-pouching of the gallbladder wall forming a mucosal fold known as "Hartmann's pouch".

Lymphatic drainage of the gallbladder follows the cystic node which is located between cystic duct and common hepatic ducts. Lymphatics from the lower part of the drain into lower hepatic lymph nodes. All the lymph finally drains into celiac lymph nodes.

Microanatomy

Micrograph of a normal gallbladder wall. H&E stain.

The gallbladder wall is composed of a number of layers. The gallbladder wall's innermost surface is lined by a single layer of columnar cells with a brush border of microvilli, very similar to intestinal absorptive cells. Underneath the epithelium is an underlying lamina propria, a muscular layer, an outer perimuscular layer and serosa. Unlike elsewhere in the intestinal tract, the gallbladder does not have a muscularis mucosae, and the muscular fibres are not arranged in distinct layers.

The mucosa, the inner portion of the gallbladder wall, consists of a lining of a single layer of columnar cells, with cells possessing small hair-like attachments called microvilli. This sits on a thin layer of connective tissue, the lamina propria. The mucosa is curved and collected into tiny outpouchings called rugae.

A muscular layer sits beneath the mucosa. This is formed by smooth muscle, with fibres that lie in longitudinal, oblique and transverse directions, and are not arranged in separate layers. The muscle fibres here contract to expel bile from the gallbladder. A distinctive feature of the gallbladder is the presence of Rokitansky–Aschoff sinuses, deep outpouchings of the mucosa that can extend through the muscular layer, and which indicate adenomyomatosis. The muscular layer is surrounded by a layer of connective and fat tissue.

The outer layer of the fundus of gallbladder, and the surfaces not in contact with the liver, are covered by a thick serosa, which is exposed to the peritoneum. The serosa contains blood vessels and lymphatics. The surfaces in contact with the liver are covered in connective tissue.

Variation

Abdominal ultrasonography showing gallbladder and common bile

The gallbladder varies in size, shape, and position between different people. Rarely, two or even three gallbladders may coexist, either as separate bladders draining into the cystic duct, or sharing a common branch that drains into the cystic duct. Additionally, the gallbladder may fail to form at all. Gallbladders with two lobes separated by a septum may also exist. These abnormalities are not likely to affect function and are generally asymptomatic.

The location of the gallbladder in relation to the liver may also vary, with documented variants including gallbladders found within, above, on the left side of, behind, and detached or suspended from the liver. Such variants are very rare: from 1886 to 1998, only 110 cases of left-lying liver, or less than one per year, were reported in scientific literature.

An anatomical variation can occur, known as a Phrygian cap, which is an innocuous fold in the fundus, named after its resemblance to the Phrygian cap.

Development

The gallbladder develops from an endodermal outpouching of the embryonic gut tube. Early in development, the human embryo has three germ layers and abuts an embryonic yolk sac. During the second week of embryogenesis, as the embryo grows, it begins to surround and envelop portions of this sac. The enveloped portions form the basis for the adult gastrointestinal tract. Sections of this foregut begin to differentiate into the organs of the gastrointestinal tract, such as the esophagus, stomach, and intestines.

During the fourth week of embryological development, the stomach rotates. The stomach, originally lying in the midline of the embryo, rotates so that its body is on the left. This rotation also affects the part of the gastrointestinal tube immediately below the stomach, which will go on to become the duodenum. By the end of the fourth week, the developing duodenum begins to spout a small outpouching on its right side, the hepatic diverticulum, which will go on to become the biliary tree. Just below this is a second outpouching, known as the cystic diverticulum, that will eventually develop into the gallbladder.

Function

1. Bile ducts: 2. Intrahepatic bile ducts, 3. Left and right hepatic ducts, 4. Common hepatic duct, 5. Cystic duct, 6. Common bile duct, 7. Ampulla of Vater, 8. Major duodenal papilla
9. Gallbladder, 10–11. Right and left lobes of liver. 12. Spleen.
13. Esophagus. 14. Stomach. 15. Pancreas: 16. Accessory pancreatic duct, 17. Pancreatic duct.
18. Small intestine: 19. Duodenum, 20. Jejunum
21–22. Right and left kidneys.
The front border of the liver has been lifted up (brown arrow).^[14]

The main function of the gallbladder is to store bile, also called gall, needed for the digestion of fats in food. Produced by the liver, bile flows through small vessels into the larger hepatic ducts and ultimately through the cystic duct (parts of the biliary tree) into the gallbladder, where it is stored. At any one time, 30 to 60 millilitres (1.0 to 2.0 US fl oz) of bile is stored within the gallbladder.

When food containing fat enters the digestive tract, it stimulates the secretion of cholecystokinin (CCK) from I cells of the duodenum and jejunum. In response to cholecystokinin, the gallbladder rhythmically contracts and releases its contents into the common bile duct, eventually draining into the duodenum. The bile emulsifies fats in partly digested food, thereby assisting their absorption. Bile consists primarily of water and bile salts, and also acts as a means of eliminating bilirubin, a product of hemoglobin metabolism, from the body.

The bile that is secreted by the liver and stored in the gallbladder is not the same as the bile that is secreted by the gallbladder. During gallbladder storage of bile, it is concentrated 3-10 fold by removal of some water and electrolytes. This is through the active transport of sodium and chloride ions across the epithelium of the gallbladder, which creates an osmotic pressure that also causes water and other electrolytes to be reabsorbed.

Clinical significance

Gallstones

3D still showing Gallstones.

Gallstones form when the bile is saturated, usually with either cholesterol or bilirubin. Most gallstones do not cause symptoms, with stones either remaining in the gallbladder or passed along the biliary system. When symptoms occur, severe "colicky" pain in the upper right part of the abdomen is often felt. If the stone blocks the gallbladder, inflammation known as cholecystitis may result. If the stone lodges in the biliary system, jaundice may occur; and if the stone blocks the pancreatic duct, then pancreatitis may occur. Gallstones are diagnosed using ultrasound. When a symptomatic gallstone occurs, it is often managed by waiting for it to be passed naturally. Given the likelihood of recurrent gallstones, surgery to remove the gallbladder is often considered. Some medication, such as ursodeoxycholic acid, may be used; and lithotripsy, a procedure used to break down the stones, may also be used.

Inflammation

Known as cholecystitis, inflammation of the gallbladder is commonly caused by obstruction of the duct with gallstones, which is known as cholelithiasis. Blocked bile accumulates, and pressure on the gallbladder wall, may lead to the release of substances that cause inflammation, such as phospholipase. There is also the risk of bacterial infection. An inflamed gallbladder is likely to cause pain and fever, and tenderness in the upper, right corner of the abdomen, and may have a positive Murphy's sign. Cholecystitis is often managed with rest and antibiotics, particularly cephalosporins and, in severe cases, metronidazole.

Gallbladder removal

A cholecystectomy is a procedure in which the gallbladder is removed. It may be removed because of recurrent gallstones, and is considered an elective procedure. A cholecystectomy may be an open procedure, or one conducted by laparoscopy. In the surgery, the gallbladder is removed from the neck to the fundus, and so bile will drain directly from the liver into the biliary tree. About 30 percent of patients may experience some degree of indigestion following the procedure, although severe complications are much rarer. About 10 percent of surgeries lead to a chronic condition of postcholecystectomy syndrome.

Complication

Biliary injury (bile duct injury) is the traumatic damage of the bile ducts. It is most commonly an iatrogenic complication of cholecystectomy — surgical removal of gall bladder, but can also be caused by other operations or by major trauma. The risk of biliary injury is more during laparoscopic cholecystectomy than during open cholecystectomy. Biliary injury may lead to several complications and may even cause death if not diagnosed in time and managed properly. Ideally biliary injury should be managed at a center with facilities and expertise in endoscopy, radiology and surgery.

Biloma is collection of bile within the abdominal cavity. It happens when there is a bile leak, for example after surgery for removing the gallbladder (laparoscopic cholecystectomy), with an incidence of 0.3–2%. Other causes are biliary surgery, liver biopsy, abdominal trauma, and, rarely, spontaneous perforation.

Cancer

Cancer of the gallbladder is uncommon and mostly occurs in later life. When cancer occurs, it is mostly of the glands lining the surface of the gallbladder (adenocarcinoma). Gallstones are thought to be linked to the formation of cancer, and other risk factors include large (>1 cm) gallbladder polyps and having a highly calcified "porcelain" gallbladder.

Cancer of the gallbladder can cause attacks of biliary pain, yellowing of the skin (jaundice), and weight loss. A large gallbladder may be able to be felt in the abdomen. Liver function tests may be elevated, particularly involving GGT and ALP, with ultrasound and CT scans being considered medical imaging investigations of choice. Cancer of the gallbladder is managed by removing the gallbladder, however As of 2010 the prognosis remains poor.

Cancer of the gallbladder may also be found incidentally after surgical removal of the gallbladder, with 1-3% of cancers identified in this way. Gallbladder polyps are mostly benign growths or lesions resembling growths that form in the gallbladder wall and are only associated with cancer when they are larger in size (>1 cm). Cholesterol polyps, often associated with cholesterolosis ("strawberry gallbladder", a change in the gallbladder wall due to excess cholesterol), often cause no symptoms and are thus often detected in this way.

Tests

Abdominal ultrasonography showing biliary sludge and gallstones.

Tests used to investigate for gallbladder disease include blood tests and medical imaging. A full blood count may reveal an increased white cell count suggestive of inflammation or infection. Tests such as bilirubin and liver function tests may reveal if there is inflammation linked to the biliary tree or gallbladder, and whether this is associated with inflammation of the liver, and a lipase or amylase may be elevated if there is pancreatitis. Bilirubin may rise when there is obstruction of the flow of bile. A CA 19-9 level may be taken to investigate for cholangiocarcinoma.

Ultrasound is often the first medical imaging test performed when gallbladder disease such as gallstones are suspected. An abdominal X-ray or CT scan is another form of imaging that may be used to examine the gallbladder and surrounding organs. Other imaging options include MRCP (magnetic resonance cholangiopancreatography), ERCP and percutaneous or intraoperative cholangiography. A cholescintigraphy scan is a nuclear imaging procedure used to assess the condition of the gallbladder.

Society and culture

To have 'gall' is associated with bold behaviour, whereas to have 'bile' is associated with bitterness.

In the Chinese language, the gallbladder (Chinese: 膽) is associated with courage and a myriad of related idioms, including using terms such as "a body completely [of] gall" (Chinese: 渾身是膽) to describe a brave person, and "single gallbladder hero" (Chinese: 孤膽英雄) to describe a lone hero.

In the Zangfu theory of Chinese medicine, the gallbladder not only has a digestive role, but is seen as the seat of decision-making.

Other animals

Most vertebrates have gallbladders, but the form and arrangement of the bile ducts may vary considerably. In many species, for example, there are several separate ducts running to the intestine, rather than the single common bile duct found in humans. Several species of mammals (including horses, deer, rats, and laminoids), several species of birds, lampreys and all invertebrates lack a gallbladder altogether.

The bile from several species of bears is used in traditional Chinese medicine; bile bears are kept alive in captivity while their bile is painfully extracted, in an industry characterized by animal cruelty.

History

Depictions of the gallbladder and biliary tree are found in Babylonian models found from 2000 BCE, and in ancient Etruscan model from 200 BCE, with models associated with divine worship.

Diseases of the gallbladder have been recorded in humans since antiquity, with gallstones found in the mummy of Princess Amenen of Thebes dating to 1500 BCE. Some historians believe the death of Alexander the Great may have been associated with an acute episode of cholecystitis. The existence of the gallbladder has been noted since the 5th century, but it is only relatively recently that the function and the diseases of the gallbladder has been documented, particularly in the last two centuries.

The first descriptions of gallstones appear to have been in the Renaissance, perhaps because of the low incidence of gallstones in earlier times owing to a diet with more cereals and vegetables, and less meat. Anthonius Benevinius in 1506 was the first to draw a connection between symptoms and the presence of gallstones. Courvoisier after examining a number of cases in 1890 that gave rise to the eponymous Courvoisier's law stating that in an enlarged, nontender gallbladder, the cause of jaundice is unlikely to be gallstones.

The first surgical removal of a gallstone (cholecystolithotomy) was in 1676 by physician Joenisius, who removed the stones from a spontaneously occurring biliary fistula. Stough Hobbs in 1867 performed the first recorded cholecystotomy, although such an operation was in fact described earlier by French surgeon Jean Louis Petit in the mid eighteenth century. German surgeon Carl Langenbuch performed the first cholecystectomy in 1882 for a sufferer of cholelithiasis. Before this, surgery had focused on creating a fistula for drainage of gallstones. Langenbuch reasoned that given several other species of mammal have no gallbladder, humans could survive without one.

The debate whether surgical removal of the gallbladder or simply gallstones was preferred was settled in the 1920s, with consensus that removal of the gallbladder was preferred. It was only in the mid and late parts of the twentieth century that medical imaging techniques such as use of contrast medium and CT scans were used to view the gallbladder. The first laparoscopic cholecystectomy performed by Erich Mühe of Germany in 1985, although French surgeons Phillipe Mouret and Francois Dubois are often credited for their operations in 1987 and 1988 respectively.

Stomach cancer

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Stomach_cancer 

 

Stomach cancer
Other names	Gastric cancer
A stomach ulcer that was diagnosed as cancer on biopsy and surgically removed
Specialty	Oncology
Symptoms	Early: Heartburn, upper abdominal pain, nausea, loss of appetite. Later: Weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing, blood in the stool
Usual onset	Over years
Types	Gastric carcinomas, lymphoma, mesenchymal tumor
Causes	Helicobacter pylori, genetics
Risk factors	Smoking, dietary factors such as pickled vegetables, obesity
Diagnostic method	Biopsy done during endoscopy
Prevention	Mediterranean diet, stopping smoking
Treatment	Surgery, chemotherapy, radiation therapy, targeted therapy
Prognosis	Five-year survival rate: < 10% (advanced cases), 32% (US), 71% (Japan)
Frequency	3.5 million (2015)
Deaths	783,000 (2018)

Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes including gastric adenocarcinomas. Lymphomas and mesenchymal tumors may also develop in the stomach. Early symptoms may include heartburn, upper abdominal pain, nausea and loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing and blood in the stool among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen and lymph nodes.

The most common cause is infection by the bacterium Helicobacter pylori, which accounts for more than 60% of cases. Certain types of H. pylori have greater risks than others. Smoking, dietary factors such as pickled vegetables and obesity are other risk factors. About 10% of cases run in families, and between 1% and 3% of cases are due to genetic syndromes inherited from a person's parents such as hereditary diffuse gastric cancer. Most of the time, stomach cancer develops in stages over years. Diagnosis is usually by biopsy done during endoscopy. This is followed by medical imaging to determine if the disease has spread to other parts of the body. Japan and South Korea, two countries that have high rates of the disease, screen for stomach cancer.

A Mediterranean diet lowers the risk of stomach cancer, as does the stopping of smoking. There is tentative evidence that treating H. pylori decreases the future risk. If stomach cancer is treated early, it can be cured. Treatments may include some combination of surgery, chemotherapy, radiation therapy and targeted therapy. If treated late, palliative care may be advised. Some types of lymphoma can be cured by eliminating H. pylori. Outcomes are often poor, with a less than 10% five-year survival rate in the Western world for advanced cases. This is largely because most people with the condition present with advanced disease. In the United States, five-year survival is 31.5%, while in South Korea it is over 65% and Japan over 70%, partly due to screening efforts.

Globally, stomach cancer is the fifth leading type of cancer and the third leading cause of death from cancer, making up 7% of cases and 9% of deaths. In 2018, it newly occurred in 1.03 million people and caused 783,000 deaths. Before the 1930s, in much of the world, including most Western developed countries, it was the most common cause of death from cancer. Rates of death have been decreasing in many areas of the world since then. This is believed to be due to the eating of less salted and pickled foods as a result of the development of refrigeration as a method of keeping food fresh. Stomach cancer occurs most commonly in East Asia and Eastern Europe. It occurs twice as often in males as in females.

Signs and symptoms

Endoscopic image of linitis plastica, a type of stomach cancer where the entire stomach is invaded, leading to a leather bottle-like appearance with blood coming out of it

 

Endoscopic images of the stomach cancer in early stage. Its histology was poorly differentiated adenocarcinoma with signet ring cells. Left above: normal, right above: FICE, left low: acetate stained, right low: AIM stained

 

Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (symptoms that may also be present in other related or unrelated disorders) in its early stages. By the time symptoms occur, the cancer has often reached an advanced stage (see below) and may have metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis. Stomach cancer can cause the following signs and symptoms:

Early cancers may be associated with indigestion or a burning sensation (heartburn). However, fewer than 1 in every 50 people referred for endoscopy due to indigestion has cancer. Abdominal discomfort and loss of appetite, especially for meat, can occur.

Gastric cancers that have enlarged and invaded normal tissue can cause weakness, fatigue, bloating of the stomach after meals, abdominal pain in the upper abdomen, nausea and occasional vomiting, diarrhea or constipation. Further enlargement may cause weight loss or bleeding with vomiting blood or having blood in the stool, the latter apparent as black discolouration (melena) and sometimes leading to anemia. Dysphagia suggests a tumour in the cardia or extension of the gastric tumour into the esophagus. 

These can be symptoms of other problems such as a stomach virus, gastric ulcer, or tropical sprue.

Causes

Gastric cancer occurs as a result of many factors. It occurs twice as commonly in males as females. Estrogen may protect women against the development of this form of cancer.

Infections

Helicobacter pylori infection is an essential risk factor in 65–80% of gastric cancers, but only 2% of people with Helicobacter infections develop stomach cancer. The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA. It was estimated that Epstein–Barr virus is responsible for 84,000 cases per year. AIDS is also associated with elevated risk.

Smoking

Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus. Some studies show increased risk with alcohol consumption as well.

Diet

Sequence of 123-iodine human scintiscans after an intravenous injection: (from left) after 30 minutes, 20 hours and 48 hours. A high and rapid concentration of radio-iodine is evident in gastric mucosa of the stomach, in salivary glands, oral mucosa and in the periencephalic and cerebrospinal fluid (left). In the thyroid gland, I-concentration is more progressive, also in the reservoir (from 1% after 30 minutes to 5.8 % after 48 hours, of the total injected dose).^[33]

Dietary factors are not proven causes, and the association between stomach cancer and various foods and beverages is weak. Some foods including smoked foods, salt and salt-rich foods, red meat, processed meat, pickled vegetables, and bracken are associated with a higher risk of stomach cancer. Nitrates and nitrites in cured meats can be converted by certain bacteria, including H. pylori, into compounds that have been found to cause stomach cancer in animals.

Fresh fruit and vegetable intake, citrus fruit intake, and antioxidant intake are associated with a lower risk of stomach cancer. A Mediterranean diet is associated with lower rates of stomach cancer, as is regular aspirin use.

Obesity is a physical risk factor that has been found to increase the risk of gastric adenocarcinoma by contributing to the development of gastroesophageal reflux disease (GERD). The exact mechanism by which obesity causes GERD is not completely known. Studies hypothesize that increased dietary fat leading to increased pressure on the stomach and the lower esophageal sphincter, due to excess adipose tissue, could play a role, yet no statistically significant data has been collected. However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than 2 times for an obese person. There is a correlation between iodine deficiency and gastric cancer.

Genetics

About 10% of cases run in families and between 1% and 3% of cases are due to genetic syndromes inherited from a person's parents such as hereditary diffuse gastric cancer.

A genetic risk factor for gastric cancer is a genetic defect of the CDH1 gene known as hereditary diffuse gastric cancer (HDGC). The CDH1 gene, which codes for E-cadherin, lies on the 16th chromosome. When the gene experiences a particular mutation, gastric cancer develops through a mechanism that is not fully understood. This mutation is considered autosomal dominant meaning that half of a carrier's children will likely experience the same mutation. Diagnosis of hereditary diffuse gastric cancer usually takes place when at least two cases involving a family member, such as a parent or grandparent, are diagnosed, with at least one diagnosed before the age of 50. The diagnosis can also be made if there are at least three cases in the family, in which case age is not considered.

The International Cancer Genome Consortium is leading efforts to identify genomic changes involved in stomach cancer. A very small percentage of diffuse-type gastric cancers (see Histopathology below) arise from an inherited abnormal CDH1 gene. Genetic testing and treatment options are available for families at risk.

Other

Other risks include diabetes, pernicious anemia, chronic atrophic gastritis, Menetrier's disease (hyperplastic, hypersecretory gastropathy), and intestinal metaplasia.

Diagnosis

To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:

• Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fibre optic camera into the stomach to visualise it.
• Upper GI series (may be called barium roentgenogram).
• Computed tomography or CT scanning of the abdomen may reveal gastric cancer. It is more useful to determine invasion into adjacent tissues or the presence of spread to local lymph nodes. Wall thickening of more than 1 cm that is focal, eccentric and enhancing favours malignancy.

In 2013, Chinese and Israeli scientists reported a successful pilot study of a breathalyzer-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive endoscopy. A larger-scale clinical trial of this technology was completed in 2014.

Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.

Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualise cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are being tested investigationally for similar applications.

A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include tripe palms (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses.

Various blood tests may be done including a complete blood count (CBC) to check for anaemia, and a fecal occult blood test to check for blood in the stool.

Histopathology

• Gastric adenocarcinoma is a malignant epithelial tumour, originating from glandular epithelium of the gastric mucosa. Stomach cancers are about 90% adenocarcinomas. Histologically, there are two major types of gastric adenocarcinoma (Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the muscularis mucosae, the submucosa and then the muscularis propria. Intestinal type adenocarcinoma tumour cells describe irregular tubular structures, harbouring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighbouring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica or leather-bottle stomach) tumour cells are discohesive and secrete mucus, which is delivered in the interstitium, producing large pools of mucus/colloid (optically "empty" spaces). It is poorly differentiated. If the mucus remains inside the tumour cell, it pushes the nucleus to the periphery: "signet-ring cell".
• Around 5% of gastric cancers are lymphomas. These may include extranodal marginal zone B-cell lymphomas (MALT type) and to a lesser extent diffuse large B-cell lymphomas. MALT type make up about half of stomach lymphomas.
• Carcinoid and stromal tumors may occur.

• 

  Poor to moderately differentiated adenocarcinoma of the stomach. H&E stain.
  
• 

  Gastric signet ring cell carcinoma. H&E stain.
  
• 

  Adenocarcinoma of the stomach and intestinal metaplasia. H&E stain.
  

Staging

T stages of stomach cancer

If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread and, if so, what parts of the body are affected. Because stomach cancer can spread to the liver, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.

Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.

The clinical stages of stomach cancer are:

• Stage 0. Limited to the inner lining of the stomach. Treatable by endoscopic mucosal resection when found very early (in routine screenings); otherwise by gastrectomy and lymphadenectomy without need for chemotherapy or radiation.
• Stage I. Penetration to the second or third layers of the stomach (Stage 1A) or to the second layer and nearby lymph nodes (Stage 1B). Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (5-fluorouracil) and radiation therapy.
• Stage II. Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes. Treated as for Stage I, sometimes with additional neoadjuvant chemotherapy.
• Stage III. Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes. Treated as for Stage II; a cure is still possible in some cases.
• Stage IV. Cancer has spread to nearby tissues and more distant lymph nodes, or has metastasized to other organs. A cure is very rarely possible at this stage. Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide, docetaxel, oxaliplatin, capecitabine or irinotecan.

Stomach cancer metastasized to the lungs

The TNM staging system is also used.

In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in Stage I 17% in Stage II, and 28% in Stage III. A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III. However, in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.

Prevention

Getting rid of H. pylori in those who are infected decreases the risk of stomach cancer, at least in those who are Asian. A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.

Management

Cancer of the stomach is difficult to cure unless it is found at an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made.

Treatment for stomach cancer may include surgery, chemotherapy, or radiation therapy. New treatment approaches such as immunotherapy or gene therapy and improved ways of using current methods are being studied in clinical trials.

Surgery

Anatomy before Roux-en-y surgery to resect stomach cancer.

Surgery remains the only curative therapy for stomach cancer. Of the different surgical techniques, endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that was pioneered in Japan and is available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection. A 2016 Cochrane review found low quality evidence of no difference in short-term mortality between laparoscopic and open gastrectomy (removal of stomach), and that benefits or harms of laparoscopic gastrectomy cannot be ruled out. Post-operatively, up to 70% of people undergoing total gastrectomy develop complications such as dumping syndrome and reflux esophagitis. Construction of a "pouch", which serves as a "stomach substitute", reduced the incidence of dumping syndrome and reflux esophagitis by 73% and 63% respectively, and led to improvements in quality-of-life, nutritional outcomes, and body mass index.

Those with metastatic disease at the time of presentation may receive palliative surgery and while it remains controversial, due to the possibility of complications from the surgery itself and the fact that it may delay chemotherapy the data so far is mostly positive, with improved survival rates being seen in those treated with this approach.

Chemotherapy

The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease and increase survival time. Some drugs used in stomach cancer treatment have included: 5-FU (fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU (semustine) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells.

Targeted therapy

Recently, treatment with human epidermal growth factor receptor 2 (HER2) inhibitor, trastuzumab, has been demonstrated to increase overall survival in inoperable locally advanced or metastatic gastric carcinoma over-expressing the HER2/neu gene. In particular, HER2 is overexpressed in 13–22% of patients with gastric cancer. Of note, HER2 overexpression in gastric neoplasia is heterogeneous and comprises a minority of tumor cells (less than 10% of gastric cancers overexpress HER2 in more than 5% of tumor cells). Hence, this heterogeneous expression should be taken into account for HER2 testing, particularly in small samples such as biopsies, requiring the evaluation of more than one bioptic sample.

Radiation

Radiation therapy (also called radiotherapy) may be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.

Lymphoma

Lymphoma of the MALT type can often be fully treated by treating an underlying H. pylori infection. This results in remission in about 80% of cases.

Prognosis

The prognosis of stomach cancer is generally poor, due to the fact the tumour has often metastasised by the time of discovery and the fact that most people with the condition are elderly (median age is between 70 and 75 years) at presentation. The average life expectancy after being diagnosed is around 24 months, and the five-year survival rate for stomach cancer is less than 10 percent.

Almost 300 genes are related to outcomes in stomach cancer with both unfavorable genes where high expression related to poor survival and favorable genes where high expression associated with longer survival times. Examples of poor prognosis genes include ITGAV and DUSP1.

Epidemiology

Stomach cancer deaths per million persons in 2012

  0–11

  12–16

  17–24

  25–33

  34–51

  52–76

  77–102

  103–128

  129–175

  176–400

Worldwide, stomach cancer is the fifth most-common cancer with 952,000 cases diagnosed in 2012. It is more common both in men and in developing countries. In 2012, it represented 8.5% of cancer cases in men, making it the fourth most-common cancer in men. Also in 2012, the number of deaths was 700,000 having decreased slightly from 774,000 in 1990, making it the third-leading cause of cancer-related death (after lung cancer and liver cancer).

Less than 5% of stomach cancers occur in people under 40 years of age with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29.

In 2014, stomach cancer resulted in 0.61% of deaths (13,303 cases) in the U.S. In China, stomach cancer accounted for 3.56% of all deaths (324,439 cases). The highest rate of stomach cancer was in Mongolia, at 28 cases per 100,000 people.

In the United Kingdom, stomach cancer is the fifteenth most-common cancer (around 7,100 people were diagnosed with stomach cancer in 2011), and it is the tenth most-common cause of cancer-related deaths (around 4,800 people died in 2012).

Incidence and mortality rates of gastric cancer vary greatly in Africa. The GLOBOCAN system is currently the most widely used method to compare these rates between countries, but African incidence and mortality rates are seen to differ among countries, possibly due to the lack of universal access to a registry system for all countries. Variation as drastic as estimated rates from 0.3/100000 in Botswana to 20.3/100000 in Mali have been observed. In Uganda, the incidence of gastric cancer has increased from the 1960s measurement of 0.8/100000 to 5.6/100000. Gastric cancer, though present, is relatively low when compared to countries with high incidence like Japan and China. One suspected cause of the variation within Africa and between other countries is due to different strains of the Helicobacter pylori bacteria. The trend commonly-seen is that H. pylori infection increases the risk for gastric cancer. However, this is not the case in Africa, giving this phenomenon the name the “African enigma.” Although this bacteria is found in Africa, evidence has supported that different strains with mutations in the bacterial genotype may contribute to the difference in cancer development between African countries and others outside the continent. However, increasing access to health care and treatment measures have been commonly-associated with the rising incidence, particularly in Uganda.

Other animals

The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas but other histological types have been reported. Signs vary but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. In order to determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasound may be performed. Gastroscopy, a test using an instrument called endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy. Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.