Intestinal metaplasia

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Intestinal metaplasia
Histopathology of Barrett's esophagus, annotated.jpg
Histopathology of Barrett's esophagus, showing intestinalized epithelium with Goblet cells, as opposed to normal stratified squamous epithelium of the esophagus, and pseudostratified columnar epithelium of the fundus of the stomach. H&E stain.

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 inflammation caused by H. pylori infection in the stomach and GERD in the esophagus are seen as the primary instigators of metaplasia and subsequent adenocarcinoma formation. Initially, the transformed epithelium resembles the small intestine lining; in the later stages it resembles the lining of the colon. It is characterized by the appearance of goblet cells and expression of intestinal cell markers such as the transcription factor, CDX2.

Contents

Risk factors

Although it was originally reported that people of East Asian ethnicity with gastric intestinal metaplasia are at increased risk of stomach cancer, [1] it is now clear that gastric intestinal metaplasia is also a risk factor in low-incidence regions like Europe. [2] Risk factors for progression of gastric intestinal metaplasia to full blown cancer are smoking and family history. [3]

Latency

Intestinal metaplasia lesions that have an active DNA damage response are likely to experience extended latency in the premalignant state until the incidence of damages overrides the DNA damage response leading to clonal expansion and progression to cancer. [4] During the DNA damage response, proteins are expressed that detect DNA damages and activate downstream responses like DNA repair, cell cycle checkpoints or apoptosis. [4]

Related Research Articles

<span class="mw-page-title-main">Esophagus</span> Vertebrate organ through which food passes to the stomach

The esophagus or oesophagus, colloquially known also as the food pipe, food tube, or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the stomach. The esophagus is a fibromuscular tube, about 25 cm (10 in) long in adults, that travels behind the trachea and heart, passes through the diaphragm, and empties into the uppermost region of the stomach. During swallowing, the epiglottis tilts backwards to prevent food from going down the larynx and lungs. The word oesophagus is from Ancient Greek οἰσοφάγος (oisophágos), from οἴσω (oísō), future form of φέρω + ἔφαγον.

<span class="mw-page-title-main">Barrett's esophagus</span> Medical condition

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 cells that are normally present only in the small intestine and large intestine. This change is considered to be a premalignant condition because of its potential to further transition to esophageal adenocarcinoma, an often-deadly cancer.

<span class="mw-page-title-main">Esophageal cancer</span> Gastrointestinal system cancer that is located in the esophagus

Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice, enlarged lymph nodes ("glands") around the collarbone, a dry cough, and possibly coughing up or vomiting blood.

<span class="mw-page-title-main">Stomach cancer</span> Cancerous tumor originating in the stomach lining

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.

<span class="mw-page-title-main">Gastritis</span> Stomach disease that is an inflammation of the lining of the stomach

Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain. Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn. Complications may include stomach bleeding, stomach ulcers, and stomach tumors. When due to autoimmune problems, low red blood cells due to not enough vitamin B12 may occur, a condition known as pernicious anemia.

<span class="mw-page-title-main">Familial adenomatous polyposis</span> Pre-cancerous intestinal polyps

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 cancer occurs when they are left untreated. Three variants are known to exist, FAP and attenuated FAP are caused by APC gene defects on chromosome 5 while autosomal recessive FAP is caused by defects in the MUTYH gene on chromosome 1. Of the three, FAP itself is the most severe and most common; although for all three, the resulting colonic polyps and cancers are initially confined to the colon wall. Detection and removal before metastasis outside the colon can greatly reduce and in many cases eliminate the spread of cancer.

<span class="mw-page-title-main">Metaplasia</span> Medical condition

Metaplasia is the transformation of a cell type to another cell type. The change from one type of cell to another may be part of a normal maturation process, or caused by some sort of abnormal stimulus. In simplistic terms, it is as if the original cells are not robust enough to withstand their environment, so they transform into another cell type better suited to their environment. If the stimulus causing metaplasia is removed or ceases, tissues return to their normal pattern of differentiation. Metaplasia is not synonymous with dysplasia, and is not considered to be an actual cancer. It is also contrasted with heteroplasia, which is the spontaneous abnormal growth of cytologic and histologic elements. Today, metaplastic changes are usually considered to be an early phase of carcinogenesis, specifically for those with a history of cancers or who are known to be susceptible to carcinogenic changes. Metaplastic change is thus often viewed as a premalignant condition that requires immediate intervention, either surgical or medical, lest it lead to cancer via malignant transformation.

<span class="mw-page-title-main">Atrophic gastritis</span> Medical condition

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 of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency possibly leading to pernicious anemia; and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with autoimmune atrophic gastritis (Type A gastritis) are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria.

Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract and accessory 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, abnormal bleeding or other associated problems. The diagnosis often requires endoscopy, followed by biopsy 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.

<span class="mw-page-title-main">G cell</span> Type of cell in the stomach and duodenum that secretes gastrin

In anatomy, the G cell or gastrin cell is a type of cell in the stomach and duodenum that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells. G cells are found deep within the pyloric glands of the stomach antrum, and occasionally in the pancreas and duodenum. The vagus nerve innervates the G cells. Gastrin-releasing peptide is released by the post-ganglionic fibers of the vagus nerve onto G cells during parasympathetic stimulation. The peptide hormone bombesin also stimulates gastrin from G cells. Gastrin-releasing peptide, as well as the presence of amino acids in the stomach, stimulates the release of gastrin from the G cells. Gastrin stimulates enterochromaffin-like cells to secrete histamine. Gastrin also targets parietal cells by increasing the amount of histamine and the direct stimulation by gastrin, causing the parietal cells to increase HCl secretion in the stomach. G-cells frequently express PD-L1 during homeostasis which protects them from Helicobacter pylori-induced immune destruction

<span class="mw-page-title-main">Small intestine cancer</span> Medical condition

Small intestine cancer starts when cells in the small intestine start to grow out of control. The small intestine is the largest part of the gastrointestinal tract, which processes food for energy and rids the body of solid waste. The small intestine is not as common as other cancers of the GI tract such as colon, rectal, stomach, and esophageal cancers in the United States. They account for fewer than 1 in 10 cancers in the GI tract, and fewer than 1 in 100 cancers overall.

Esophageal dysphagia is a form of dysphagia where the underlying cause arises from the body of the esophagus, lower esophageal sphincter, or cardia of the stomach, usually due to mechanical causes or motility problems.

<span class="mw-page-title-main">CDX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The CDX2 protein is a homeobox transcription factor expressed in the nuclei of intestinal epithelial cells, playing an essential role in the development and function of the digestive system. CDX2 is part of the ParaHox gene cluster, a group of three highly conserved developmental genes present in most vertebrate species. Together with CDX1 and CDX4, CDX2 is one of three caudal-related genes in the human genome.

<span class="mw-page-title-main">Signet ring cell carcinoma</span> Medical condition

Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells.

Norman Rupert Barrett CBE FRSA was an Australian-born British thoracic surgeon who is widely yet mistakenly remembered for describing what became known as Barrett's oesophagus.

<span class="mw-page-title-main">Sessile serrated lesion</span> Medical condition

A sessile serrated lesion (SSL) is a premalignant flat lesion of the colon, predominantly seen in the cecum and ascending colon.

<span class="mw-page-title-main">Chromoendoscopy</span>

Chromoendoscopy is a medical procedure wherein dyes are instilled into the gastrointestinal tract at the time of visualization with fibre-optic endoscopy. The purposes of chromoendoscopy is chiefly enhance the characterization of tissues, although dyes may be used for other functional purposes. The detail achieved with chromoendoscopy can often allow for identification of the tissue type or pathology based upon the pattern uncovered.

Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy.

<span class="mw-page-title-main">Field cancerization</span> Biological process

Field cancerization or field effect is a biological process in which large areas of cells at a tissue surface or within an organ are affected by carcinogenic alterations. The process arises from exposure to an injurious environment, often over a lengthy period.

Gastrointestinal intraepithelial neoplasia is also known as gastrointestinal dysplasia. Gastrointestinal dysplasia refers to abnormal growth of the epithelial tissue lining the gastrointestinal tract including the esophagus, stomach, and colon. Pancreatic, biliary, and rectal Intraepithelial Neoplasia are discussed separately. The regions of abnormal growth are confined by the basement membrane adjacent to the epithelial tissue and are thought to represent pre-cancerous lesions. 

References

  1. Choi, AY; Strate, LL; Fix, MC; Schmidt, RA; Ende, AR; Yeh, MM; Inadomi, JM; Hwang, JH (April 2018). "Association of gastric intestinal metaplasia and East Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population". Gastrointestinal Endoscopy. 87 (4): 1023–1028. doi:10.1016/j.gie.2017.11.010. PMID   29155082.
  2. den Hollander WJ, Holster IL, den Hoed CM, Capelle LG, Tang TJ, Anten MP, Prytz-Berset I, Witteman EM, Ter Borg F, Hartog GD, Bruno MJ, Peppelenbosch MP, Lesterhuis W, Doukas M, Kuipers EJ, Spaander MC (April 2019). "Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions". Gut. 68 (4): 585–593. doi:10.1136/gutjnl-2017-314498. PMID   29875257. S2CID   46962160.
  3. Nieuwenburg SA, Mommersteeg MC, Eikenboom EL, Yu B, den Hollander WJ, Holster IL, den Hoed CM, Capelle LG, Tang TJ, Anten MP, Prytz-Berset I, Witteman EM, Ter Borg F, Burger JP, Bruno MJ, Fuhler GM, Peppelenbosch MP, Doukas M, Kuipers EJ, Spaander MC (March 2021). "Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions". Endosc Int Open. 9 (3): E297–E305. doi:10.1055/a-1314-6626. PMC   7892268 . PMID   33655025.
  4. 1 2 Krishnan, V; Lim, DXE; Hoang, PM; et al. (October 2020). "DNA damage signalling as an anti-cancer barrier in gastric intestinal metaplasia". Gut. 69 (10): 1738–1749. doi:10.1136/gutjnl-2019-319002. PMC   7497583 . PMID   31937549.