Рак желудочно-кишечного тракта: диагностика и лечение

Organ system cancer located in gastrointestinal tract

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. 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.]] 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. 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, genetic aspects (including a number of heritable syndromes) and infections (for example, Helicobacter pylori or Epstein Barr virus) and pernicious anemia.

Pancreatic cancer is the fifth most common cause of cancer related deaths in the United States, 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. Chronic pancreatitis, diabetes or other conditions may also be involved in their development. Pancreatic cancer tends to be aggressive, and it resists radiotherapy and chemotherapy. 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.

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. 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. Anal cancer is investigated by biopsy 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%.

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. These field defects may contain visible gross manifestations, epigenetic alterations and/or mutations.

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, and has prevalent epigenetic alterations. 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). A field defect associated with progression towards squamous cell carcinoma can be identified with epigenetic markers.

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. 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.

When a segment of the large intestine, containing a 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., 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.

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. 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.