| Gastrointestinal cancer | |
|---|---|
| Specialty | Gastroenterologyoncology |
| Symptoms | upperHematemesisMelenalowerCoffee ground vomitingHematochezia |
Gastrointestinal cancer refers tomalignant conditions of thegastrointestinal tract (GI tract) andaccessory organs of digestion, 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 requiresendoscopy, followed bybiopsy 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.[1][2] There is significant geographic variation in the rates of different gastrointestinal cancers.[1]
Esophageal cancer is the sixth-most-common cancer in the world, and its incidence is increasing.[4] Some three to five males are affected for each female.[4] 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.[1] Ethiopia also has a notably high incidence.[4] 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.[4] Patients with esophageal/esophagogastric junctionadenocarcinoma were found to have significantly greater number ofDNA adducts (DNA damages) in the distal esophagus than in a control group.[5]
Cancer of theesophagus is often detected late inasmuch as there are typically no early symptoms. Nevertheless, if the cancer is caught soon enough, patients can have afive-year survival rate 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%.[4]
Cancer of thestomach, also called gastric cancer, is the fourth-most-common type of cancer and the second-highest cause of cancer death globally.[2] 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.[6] The most common type of gastric cancer isadenocarcinoma, which causes about 750,000 deaths each year.[7] Important factors that may contribute to the development of gastric cancer include diet, smoking andalcohol consumption, genetic aspects (including a number of heritable syndromes) and infections (for example,Helicobacter pylori orEpstein-Barr virus) andpernicious anemia.[1][7] Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear.[8]
Pancreatic cancer is the fifth most-common cause of cancer-related deaths in the United States,[9] and the seventh most-common in Europe.[10] In 2008, globally there were 280,000 new cases of pancreatic cancer reported and 265,000 deaths.[11] These cancers are classified as endocrine or nonendocrine tumors. The most common is ductal adenocarcinoma.[1] The most significant risk factors for pancreatic cancer are advanced age (over 60) and smoking.[9]Chronic pancreatitis,diabetes or other conditions may also be involved in their development.[2] Early pancreatic cancer does not tend to result in any symptoms, but when a tumor is advanced, a patient may experience severe pain in the upperabdomen, possibly radiating to the back.[9] Another symptom might bejaundice, a yellowing of the skin and eyes.[10]
Pancreatic cancer has a poorprognosis,[2] with afive-year survival rate of less than 5%. By the time the cancer is diagnosed, it is usually at an advanced, inoperable stage.[10] Only one in about fifteen to twenty patients is curative surgery attempted.[12] Pancreatic cancer tends to be aggressive, and it resistsradiotherapy andchemotherapy.[11]
People get liver cancer (also calledhepatocellular carcinoma, HCC orhepatoma) typically from a prolongedHepatitis B orC infection or as a result ofcirrhosis from chronicalcoholism. Liver cancer may bring about yellowing of the skin and eyes (jaundice), itching (pruritus), or cause a buildup of fluid in the abdomen (ascites). A person may feel an enlarging mass, or the cancer might be revealed by abnormalliver function tests.[13]: 664–666
An attending practitioner might order abiopsy, anMRI or aCT scan, and a patient might be monitored through blood tests (includingalpha-fetoprotein, liver-function tests orultrasound. These cancers are typically treated according to theirTNM stage and whether or notcirrhosis is present. Options includesurgical resection,embolisation,ablation or aliver transplant.[14]: 969–970
Cancers of the gallbladder are typically adenocarcinomas, and are common in elderly women. Gallbladder cancer is strongly associated withgallstones, aporcelain gallbladder appearance onultrasound, 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 withultrasound and staged withCT. The prognosis for gallbladder cancer is poor.[14]: 981
Colorectal cancer is a disease ofold age. It typically originates in thesecretory 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 withhereditary syndromes likePeutz-Jegher's,hereditary nonpolyposis colorectal cancer, orfamilial adenomatous polyposis.[13]: 619–620 Colorectal cancer can be detected through the bleeding of apolyp,colicky bowel pain, abowel obstruction or the biopsy of apolyp at ascreeningcolonoscopy.A constant feeling of having to go to the toilet oranemia might also point to this kind of cancer.[14]: 911
Use of acolonoscope can find these cancers, and abiopsy can reveal the extent of the involvement of the bowel wall.Removal of a section of the colon is necessary for treatment, with or withoutchemotherapy. Colorectal cancer has a comparatively good prognosis when detected early.[14]: 911–912
The International Agency for Research on Cancer (IARC) that is associated with the World Health Organization (WHO) has classified processed meat as a group I carcinogen, since the IARC found sufficient evidence that human consumption of processed meat causes colorectal cancer.[15][16][17]Bile acids (released into the colon upon ingestion of meat) are also implicated as an important factor in the development of colorectal cancer.[18][19] The bile aciddeoxycholic acid is increased in the colonic contents of humans consuming a high fat diet.[18][19] In populations that have a high incidence of colorectal cancer, fecal concentrations of bile acids are higher.[18]
A 2025 meta analysis reported on the relationship of fecal bile acid concentrations to the development and progression of colorectal cancer and found that higher fecal concentrations of the bile acidscholic acid andchenodeoxycholic acid are associated with a high risk and higher incidence of colorectal cancer.[20]
An important anatomic landmark in anal cancer is thepectinate line (dentate line), which is located about 1–2 cm from theanal verge (where theanal mucosa of theanal canal becomes skin).[21] 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 mayulcerate. Anal cancer is strongly associated withulcerative colitis and thesexually transmissible infectionsHPV andHIV. Anal cancer may be a cause ofconstipation ortenesmus, or may be felt as a palpable mass, although it may occasionally present as an ulcerative form.[22]: 580
Anal cancer is investigated bybiopsy and may be treated bysurgery andradiotherapy, or with external beam radiotherapy and adjunctive chemotherapy. The five-year survival rate with the latter procedure is above 70%.[22]: 580
Agastrointestinal 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.[23]
A "field defect" or "field cancerization" is a region of tissue that precedes and predisposes to the development of cancer. Field defects occur in progression to gastrointestinal tract cancers.[24] These field defects may contain visible gross manifestations,epigenetic alterations and/or mutations.
Adenocarcinomas of the esophagus tend to arise in a field defect calledBarrett's esophagus, a red patch of tissue in the generally pink lower esophagus. A diagnosis of Barrett's esophagus is confirmed by ametaplastic change of the esophageal mucosa from squamous tocolumnar mucosa with intestinal metaplasia. Barrett's esophagus is the dominantpre-malignant lesion of esophagealadenocarcinoma,[25] and has prevalent epigenetic alterations.[26]
Esophageal squamous-cell carcinomas may occur as secondprimary tumors associated withhead and neck cancer, due tofield cancerization (i.e. a regional reaction to long-termcarcinogenic exposure).[27][28] A field defect associated with progression towards squamous cell carcinoma can be identified withepigenetic markers.[29]
Gastric cancer develops within areas (field defects) of the stomach withatrophic gastritis andintestinal metaplasia: these lesions represent the cancerization field in which (intestinal-type) gastric cancers develop.[30] In one study, the field defect was clearly demonstrated in gastric carcinogenesis usingmiRNA high throughput data from normal gastric mucosa (from patients who had never had a gastricmalignant 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.[31]
When a segment of thelarge intestine, containing acolorectal cancer, is removed, the area adjacent to the cancer (and removed with it) may show additional neoplasia in the form ofpolyps (see image). This is visual evidence of a field defect. Some of these polyps may be premalignantneoplastic tumors. As shown by Hofstad et al.,[32] 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.[33] summarized the substantial body of evidence that field cancerization occurs in the colon, often due to aberrant DNA methylation.
Bile acids are synthesized in the liver to facilitatedigestion of dietaryfats. 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.[34] The deleterious effects on cells of elevated bile acid exposure include induction ofreactive oxygen species, induction ofDNA damage leading tomutation, and induction ofapoptosis in the short term and selection for apoptosis resistance over the long term.[34] High levels of bile acids also alter the microbiome and act as signaling molecules, altering the microenvironment of the colon.[35]
