Gastrointestinal cancer refers to

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

conditions of the gastrointestinal tract (GI tract) and

accessory organs of digestion The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallbladder). Digestion involves the breakdown of food into smaller and smaller compon ...

, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The symptoms relate to the organ affected and can include obstruction (leading to difficulty swallowing or defecating), abnormal bleeding or other associated problems. The diagnosis often requires

endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...

, followed by

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...

of suspicious tissue. The treatment depends on the location of the tumor, as well as the type of cancer cell and whether it has invaded other tissues or spread elsewhere. These factors also determine the prognosis. Overall, the GI tract and the accessory organs of digestion (pancreas, liver, gall bladder) are responsible for more cancers and more deaths from cancer than any other system in the body. There is significant geographic variation in the rates of different gastrointestinal cancers.

Upper digestive tract

Esophageal cancer

Esophageal cancer is the sixth-most-common cancer in the world, and its incidence is increasing. Some three to five males are affected for each female. An "esophageal cancer belt", in which the incidence of esophageal squamous cell carcinoma (SCC) is more than a hundred times that of adjacent areas, extends from northeastern China through central Asia to northern Iran. Ethiopia also has a notably high incidence. There are two main types of esophageal cancer—adenocarcinoma and squamous cell carcinoma. Worldwide, the incidence of each type is about the same, but in developed countries like North America and Europe adenocarcinoma is the more common. Cancer of the

esophagus The esophagus ( American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to ...

is often detected late inasmuch as there are typically no early symptoms. Nevertheless, if the cancer is caught soon enough, patients can have a

five-year survival rate The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...

of 90% or above. By the time esophageal cancer is usually detected, though, it might have spread beyond the esophageal wall, and the survival rate drops significantly. In China, the overall five-year survival rate for advanced esophageal cancer is about 20%, and in the United States it is about 15%.

Stomach cancer

Cancer of the

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 ...

, also called gastric cancer, is the fourth-most-common type of cancer and the second-highest cause of cancer death globally. Eastern Asia (China, Japan, Korea, Mongolia) is a high-risk area for gastric cancer, and North America, Australia, New Zealand and western and northern Africa are areas with low risk. The most common type of gastric cancer is adenocarcinoma, which causes about 750,000 deaths each year. Important factors that may contribute to the development of gastric cancer include diet, smoking and

alcohol consumption An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The cons ...

, genetic aspects (including a number of heritable syndromes) and infections (for example, ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...

'' or Epstein-Barr virus) and

pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...

. Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear.

Pancreatic cancer

Pancreatic cancer is the fifth-most-common cause of cancer deaths in the United States, and the seventh most common in Europe. In 2008, globally there were 280,000 new cases of pancreatic cancer reported and 265,000 deaths. These cancers are classified as endocrine or nonendocrine tumors. The most common is ductal adenocarcinoma. The most significant risk factors for pancreatic cancer are advanced age (over 60) and smoking. Chronic pancreatitis,

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

or other conditions may also be involved in their development. Early pancreatic cancer does not tend to result in any symptom, but when a tumor is advanced, a patient may experience severe pain in the upper

abdomen 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 ...

, possibly radiating to the back. Another symptom might be jaundice, a yellowing of the skin and eyes. Pancreatic cancer has a poor prognosis, with a

of less than 5%. By the time the cancer is diagnosed, it is usually at an advanced, inoperable stage. Only one in about fifteen to twenty patients is curative surgery attempted. Pancreatic cancer tends to be aggressive, and it resists radiotherapy and

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. Chemothe ...

Liver cancer

People get liver cancer (also called ''hepatocellular carcinoma, HCC'' or ''hepatoma)'' typically from a prolonged

Hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...

or C infection or as a result of

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

from chronic

alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...

. Liver cancer may bring about yellowing of the skin and eyes ( jaundice), itching (

pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

), or cause a buildup of fluid in the abdomen (

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

). A person may feel an enlarging mass, or the cancer might be revealed by abnormal

liver function test Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

s. An attending practitioner might order a

, an

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 ...

or a CT scan, and a patient might be monitored through blood tests (including

alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...

, liver-function tests or

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 ...

. These cancers are typically treated according to their TNM stage and whether or not

is present. Options include surgical resection,

embolisation Embolization refers to the passage and lodging of an embolus within the circulatory system, bloodstream. It may be of natural origin (pathological), in which word sense, sense it is also called embolism, for example a pulmonary embolism; or i ...

ablation Ablation ( la, ablatio – removal) is removal or destruction of something from an object by vaporization, chipping, erosive processes or by other means. Examples of ablative materials are described below, and include spacecraft material for a ...

or a

liver transplant Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...

Gallbladder cancer

Cancers of the gallbladder are typically adenocarcinomas, and are common in elderly women. Gallbladder cancer is strongly associated with

gallstone 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 mi ...

s, a

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 ...

appearance on

, and the presence of polyps within the gallbladder. Gallbladder cancer may manifest with weight loss, jaundice, and pain in the upper right of. It is typically diagnosed with

and staged with CT. The prognosis for gallbladder cancer is poor.

Other

MALT lymphoma MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zone of the MAL ...

is a cancer of the

mucosa-associated lymphoid tissue The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tr ...

, usually in the stomach. *

Gastrointestinal stromal tumor Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior ...

s represent from 1% to 3% of gastrointestinal malignancies. * Cancers of the

biliary tree The biliary tract, (biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and co ...

, including cholangiocarcinoma.

Lower digestive tract

Colorectal cancer

Colorectal cancer is a disease of old age: It typically originates in the secretory cells lining the gut, and risk factors include diets low in vegetable fibre and high in fat. If a younger person gets such a cancer, it is often associated with hereditary syndromes like Peutz-Jegher's,

hereditary nonpolyposis colorectal cancer Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, ...

familial adenomatous polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon ...

. Colorectal cancer can be detected through the bleeding of a polyp, colicky bowel pain, a bowel obstruction or the biopsy of a polyp at a

screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...

colonoscopy. A constant feeling of having to go to the toilet or

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

might also point to this kind of cancer. Use of a

colonoscope Colonoscopy () or coloscopy () is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It can provide a visual diagnosis (''e. ...

can find these cancers, and a

can reveal the extent of the involvement of the bowel wall. Removal of a section of the colon is necessary for treatment, with or without

. Colorectal cancer has a comparatively good prognosis when detected early.

Anal cancer

An important anatomic landmark in anal cancer is the pectinate line (dentate line), which is located about 1–2 cm from the

anal verge The anal canal is the part that connects the rectum to the anus, located below the level of the pelvic diaphragm. It is located within the anal triangle of the perineum, between the right and left ischioanal fossa. As the final functional segme ...

(where the anal mucosa of the

anal canal The anal canal is the part that connects the rectum to the anus, located below the level of the pelvic diaphragm. It is located within the anal triangle of the perineum, between the right and left ischioanal fossa. As the final functional seg ...

becomes skin). Anal cancers located above this line (towards the head) are more likely to be carcinomas, whilst those located below (towards the feet) are more likely to be squamous cell carcinomas that may

ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

ate. Anal cancer is strongly associated with

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...

and the sexually transmissible infections

HPV Human papillomavirus infection (HPV infection) is caused by a DNA virus from the '' Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and re ...

and

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

. Anal cancer may be a cause of

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

or tenesmus, or may be felt as a palpable mass, although it may occasionally present as an ulcerative form. Anal cancer is investigated by

and may be treated by excision and radiotherapy, or with external beam radiotherapy and adjunctive chemotherapy. The five-year survival rate with the latter procedure is above 70%.

Gastrointestinal carcinoid tumor

A gastrointestinal carcinoid tumor is a rare, slow-growing form of cancer that affects certain cells in the lining of the stomach and intestines. The cells it affects make hormones that regulate the production of digestive juices and muscles that move food through the stomach and intestines. This kind of cancer usually occurs in the appendix, small intestine, or rectum. Its presence is associated with an increased risk of cancers affecting the other parts of the digestive system. It is usually treated with surgery.

Field defects

A "field defect" or "

field cancerization Field cancerization or field effect (also termed field change, field change cancerization, field carcinogenesis, cancer field effect or premalignant field defect) is a biological process in which large areas of cells at a tissue surface or within ...

" is a region of tissue that precedes and predisposes to the development of cancer. Field defects occur in progression to gastrointestinal tract cancers. These field defects may contain visible gross manifestations, epigenetic alterations and/or mutations.

Esophagus

Adenocarcinomas of the esophagus tend to arise in a field defect called

Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal (metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet ce ...

, a red patch of tissue in the generally pink lower esophagus. A diagnosis of Barrett’s esophagus is confirmed by a

metaplastic Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of ''individual'' synapses. However this new form re ...

change of the esophageal mucosa from squamous to

columnar 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 ...

mucosa with intestinal metaplasia. Barrett's esophagus is the dominant

pre-malignant A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...

lesion of esophageal adenocarcinoma, and has prevalent epigenetic alterations. Esophageal squamous-cell carcinomas may occur as second

primary tumor A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most cancers develop at their primary site but then go on to metastasize or spread to other parts of the body. These fur ...

s associated with

head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

, due to

(i.e. a regional reaction to long-term

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...

ic exposure). A field defect associated with progression towards squamous cell carcinoma can be identified with epigenetic markers.

Stomach

Gastric cancer develops within areas (field defects) of the stomach with

atrophic gastritis Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion o ...

and

intestinal metaplasia Intestinal metaplasia is the transformation (metaplasia) of epithelium (usually of the stomach or the esophagus) into a type of epithelium resembling that found in the intestine. In the esophagus, this is called Barrett's esophagus. Chronic inflam ...

: these lesions represent the cancerization field in which (intestinal-type) gastric cancers develop. In one study, the field defect was clearly demonstrated in gastric carcinogenesis using

miRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miR ...

high throughput data from normal gastric mucosa (from patients who had never had a gastric malignant neoplasm), non-tumor tissue adjacent to a gastric cancer, and gastric cancer tissue. Greater than five-fold reductions were found in four miRNAs in tumor-adjacent tissues and gastric cancers as compared to those miRNA levels in normal gastric tissues.

Large intestine The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before bein ...

When a segment of the large intestine, containing a

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 ...

, is removed, the area adjacent to the cancer (and removed with it) may show additional neoplasia in the form of

polyps A polyp in zoology is one of two forms found in the phylum Cnidaria, the other being the medusa. Polyps are roughly cylindrical in shape and elongated at the axis of the vase-shaped body. In solitary polyps, the aboral (opposite to oral) end i ...

(see image). This is visual evidence of a field defect. Some of these polyps may be premalignant

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

tumors. As shown by Hofstad et al., when polyps are allowed to remain in the colon and are observed for three years, about 40% of polyps are seen to grow larger, likely progressing towards cancer. Luo et al. summarized the substantial body of evidence that field cancerization occurs in the colon, often due to aberrant DNA methylation.

Etiology

Bile acids are synthesized in the liver to facilitate

digestion Digestion is the breakdown of large insoluble food molecules into small water-soluble food molecules so that they can be absorbed into the watery blood plasma. In certain organisms, these smaller substances are absorbed through the small intest ...

of dietary

fat In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food. The term often refers specifically to triglycerides (triple est ...

s. High exposure of the gastrointestinal tract to bile acids can occur in several different settings, but most significantly is prevalent among individuals who have a high dietary fat intake. High bile acid exposure has been implicated in several cancers of both the upper and lower digestive tract.Bernstein H, Bernstein C, Payne CM, Dvorak K. Bile acids as endogenous etiologic agents in gastrointestinal cancer. World J Gastroenterol. 2009 Jul 21;15(27):3329-40. doi: 10.3748/wjg.15.3329. PMID: 19610133; PMCID: PMC2712893 The deleterious effects on cells of elevated bile acid exposure include induction of

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

, induction of

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...

leading to

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

, and induction of apoptosis in the short term and selection for apoptosis resistance over the long term.

References

External links

Gastrointestinal (GI) Cancer Resource Centre

Gastrointestinal Cancer Treatment
{{DEFAULTSORT:Gastrointestinal Cancer