Gastrointestinal cancer

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Gastrointestinal cancer
Specialty Gastroenterology oncology
Symptoms upper Hematemesis Melena lower Coffee ground vomiting Hematochezia

Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract (GI 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 (leading to difficulty swallowing or defecating), 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.

Contents

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]

Upper digestive tract

Esophageal cancer

Age-standardised death rates from esophageal cancer, as reported by the WHO in 2004. Oesophagus cancer world map - Death - WHO2004.svg
Age-standardised death rates from esophageal cancer, as reported by the WHO in 2004.

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]

Cancer of the esophagus 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 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]

Stomach cancer

Cancer of the stomach, 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. [5] The most common type of gastric cancer is adenocarcinoma, which causes about 750,000 deaths each year. [6] Important factors that may contribute to the development of gastric cancer include diet, smoking and alcohol consumption, genetic aspects (including a number of heritable syndromes) and infections (for example, Helicobacter pylori or Epstein-Barr virus) and pernicious anemia. [1] [6] Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear. [7]

Pancreatic cancer

Upper and lower human gastrointestinal tract Digestive system diagram edit.svgpharynxoral cavity
Upper and lower human gastrointestinal tract

Pancreatic cancer is the fifth most-common cause of cancer-related deaths in the United States, [8] and the seventh most-common in Europe. [9] In 2008, globally there were 280,000 new cases of pancreatic cancer reported and 265,000 deaths. [10] 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. [8] 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 upper abdomen, possibly radiating to the back. [8] Another symptom might be jaundice, a yellowing of the skin and eyes. [9]

Pancreatic cancer has a poor prognosis, [2] with a five-year survival rate of less than 5%. By the time the cancer is diagnosed, it is usually at an advanced, inoperable stage. [9] Only one in about fifteen to twenty patients is curative surgery attempted. [11] Pancreatic cancer tends to be aggressive, and it resists radiotherapy and chemotherapy. [10]

Liver cancer

People get liver cancer (also called hepatocellular carcinoma, HCC or hepatoma) typically from a prolonged Hepatitis B or C infection or as a result of cirrhosis from chronic alcoholism. 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 abnormal liver function tests. [12] : 664–666 

An attending practitioner might order a biopsy, an MRI or a CT scan, and a patient might be monitored through blood tests (including alpha-fetoprotein, liver-function tests or ultrasound. These cancers are typically treated according to their TNM stage and whether or not cirrhosis is present. Options include surgical resection, embolisation, ablation or a liver transplant. [13] : 969–970 

Gallbladder cancer

Cancers of the gallbladder are typically adenocarcinomas, and are common in elderly women. Gallbladder cancer is strongly associated with gallstones, a porcelain gallbladder appearance on ultrasound, 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 ultrasound and staged with CT. The prognosis for gallbladder cancer is poor. [13] : 981 

Other

Lower digestive tract

Colorectal cancer

Example of an invasive colorectal cancer. Colon cancer 2.jpg
Example of an invasive 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, or familial adenomatous polyposis. [12] : 619–620  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 colonoscopy. A constant feeling of having to go to the toilet or anemia might also point to this kind of cancer. [13] : 911 

Use of a colonoscope can find these cancers, and a biopsy 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 chemotherapy. Colorectal cancer has a comparatively good prognosis when detected early. [13] : 911–912 

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 (where the anal mucosa of the anal canal becomes skin). [14] 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 ulcerate. Anal cancer is strongly associated with ulcerative colitis and the sexually transmissible infections HPV and HIV. Anal cancer may be a cause of constipation or tenesmus, or may be felt as a palpable mass, although it may occasionally present as an ulcerative form. [15] : 580 

Anal cancer is investigated by biopsy and may be treated by surgery and radiotherapy, or with external beam radiotherapy and adjunctive chemotherapy. The five-year survival rate with the latter procedure is above 70%. [15] : 580 

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. [16]

Field defects

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. [17] 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, a red patch of tissue in the generally pink lower esophagus. A diagnosis of Barrett's esophagus is confirmed by a metaplastic change of the esophageal mucosa from squamous to columnar mucosa with intestinal metaplasia. Barrett's esophagus is the dominant pre-malignant lesion of esophageal adenocarcinoma, [18] and has prevalent epigenetic alterations. [19]

Esophageal squamous-cell carcinomas may occur as second primary tumors associated with head and neck cancer, due to field cancerization (i.e. a regional reaction to long-term carcinogenic exposure). [20] [21] A field defect associated with progression towards squamous cell carcinoma can be identified with epigenetic markers. [22]

Stomach

Gastric cancer develops within areas (field defects) of the stomach with atrophic gastritis and intestinal metaplasia: these lesions represent the cancerization field in which (intestinal-type) gastric cancers develop. [23] In one study, the field defect was clearly demonstrated in gastric carcinogenesis using miRNA 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. [24]

Large intestine

Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors. Image of resected colon segment with cancer & 4 nearby polyps plus schematic of field defects with sub-clones.jpg
Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors.

When a segment of the large intestine, containing a colorectal cancer, is removed, the area adjacent to the cancer (and removed with it) may show additional neoplasia in the form of polyps (see image). This is visual evidence of a field defect. Some of these polyps may be premalignant neoplastic tumors. As shown by Hofstad et al., [25] 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. [26] 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 of dietary fats. 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. [27] The deleterious effects on cells of elevated bile acid exposure include induction of reactive oxygen species, induction of DNA damage leading to mutation, and induction of apoptosis in the short term and selection for apoptosis resistance over the long term. [27] High levels of bile acids also alter the microbiome and act as signaling molecules, altering the microenvironment of the colon. [28]

Related Research Articles

<span class="mw-page-title-main">Gastroenterology</span> Branch of medicine focused on the digestive system and its disorders

Gastroenterology is the branch of medicine focused on the digestive system and its disorders. The digestive system consists of the gastrointestinal tract, sometimes referred to as the GI tract, which includes the esophagus, stomach, small intestine and large intestine as well as the accessory organs of digestion which include the pancreas, gallbladder, and liver.

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

Adenocarcinoma is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.

<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">Gastrointestinal disease</span> Medical condition

Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum; and the accessory organs of digestion, the liver, gallbladder, and pancreas.

<span class="mw-page-title-main">Pancreaticoduodenectomy</span> Major surgical procedure involving the pancreas, duodenum, and other organs

A pancreaticoduodenectomy, also known as a Whipple procedure, is a major surgical operation most often performed to remove cancerous tumours from the head of the pancreas. It is also used for the treatment of pancreatic or duodenal trauma, or chronic pancreatitis. Due to the shared blood supply of organs in the proximal gastrointestinal system, surgical removal of the head of the pancreas also necessitates removal of the duodenum, proximal jejunum, gallbladder, and, occasionally, part of the stomach.

<span class="mw-page-title-main">Neoplasm</span> Tumor or other abnormal growth of tissue

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 in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.

<span class="mw-page-title-main">Precancerous condition</span> Condition or cell change indicating increased cancer risk

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 risk of developing into cancer. Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome. and cervical dysplasia, which can progress into cervical cancer. Bronchial premalignant lesions can progress to squamous cell carcinoma of the lung.

Reprimo (RPRM), is a gene located at human chromosome 2q23 whose expression in conjunction with p53, along with other genes which are p53-induced, is associated with the arrest of the cell cycle at the G2 phase. Reprimo's protein product is a highly glycosylated polypeptide which, upon its expression, is localized to the cytoplasm where it is primarily active. As the expression of reprimo is controlled by p53, which is in turn controlled by a wide array of convergent signal pathways pertaining to DNA damage or nutrient depravity, its presence is expected within cells which would cause damage should they be freely allowed to replicate. Pursuant to this, reprimo's expression during the G2 phase of the cell cycle ultimately results in the reduction of Cdc2 expression, and in the inhibition of the nuclear translocation of cyclin B1 which is necessary to its function. Reprimo is known to collaborate with p21 to achieve these specific effects, and in a more general sense collaborates with the other p53-induced proteins and effectors to produce the overall cellular response. These regulatory actions help to render the afflicted cell into an arrested state which is less immediately threatening to the whole organism due to the inability of afflicted cells to replicate with damaged DNA, among other potential circumstances, giving the cell an opportunity to undergo DNA repair or apoptosis as the level of damage will dictate. Indefinite cell cycle arrest is another potential outcome. For this reason, it is considered to be a tumor suppressor gene.

<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.

<span class="mw-page-title-main">Chromoendoscopy</span> Gastrointestinal endoscopic imaging with dyes

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.

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

A pancreatic tumor is an abnormal growth in the pancreas. In adults, almost 90% are pancreatic cancer and a few are benign. Pancreatic tumors are rare in children.

<span class="mw-page-title-main">Oesophagogastric junctional adenocarcinoma</span>

Oesophagogastric junctional adenocarcinoma is a cancer of the lower part of the oesophagus with a rising incidence in Western countries. This disease is often linked to Barrett's oesophagus.

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. 

<span class="mw-page-title-main">Squamous-cell carcinoma</span> Carcinoma that derives from squamous epithelial cells

Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts.

<span class="mw-page-title-main">CMTM3</span> Protein-coding gene in the species Homo sapiens

CKLF-like MARVEL transmembrane domain-containing protein 3, also termed chemokine-like factor superfamily 3, is a member of the CKLF-like MARVEL transmembrane domain-containing family of proteins. In humans, CMTM2 protein is encoded by the CMTM3 gene located in band 22.1 on the long arm of chromosome 16. This protein is expressed in a wide range of tissues, including fetal tissues. It is highly expressed in the male reproductive system, particularly testicular tissues and may play a role in the development of this tissue. It is also highly expressed in the immune system including circulating blood cells, i.e. B lymphocytes, CD4+ T lymphocytes, and monocytes. However, CMTM3 protein is weakly expressed or unexpressed in the malignant tissues of several types of cancers. In many but not all of theses cancers, this decreased or lack of expression appears due to methylation of the GpC islands in the promoter region, and thereby the silencing, of the CMTM3 gene.

References

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