Pathogenesis (disease development)
In approximately 85% of cases, esophageal cancer is squamous cell carcinoma. Adenocarcinomas (Barrett’s carcinoma) are present in 15% and are predominantly located in the lower portion of the esophagus. In western industrialized countries, squamous cell carcinoma has become less common as fewer and fewer people smoke. Squamous cell carcinoma of the esophagus now accounts for 80% of all cases in poorer countries. The precursor of adenocarcinoma is Barrett’s esophagus (synonym: Allison-Johnstone syndrome); this arises on the metaplastic mucosa based on esophageal peptic ulcer. Reflux esophagitis has the following three causes:
- Gastric acid secretion is so great that esophageal peristalsis can no longer cope with it
- Esophageal peristalsis is so impaired that it can not even return the normal gastric acid secretion
- The esophageal sphincter (lower sphincter of the esophagus) is insufficient (no longer closes adequately).
Most often underlying a cardia insufficiency (insufficient closure function, thereby acid gastric juice can flow back into the lower esophageal section (reflux) and cause inflammation). The condition is also frequently associated with axial hiatal hernia (sliding hernia due to diaphragmatic hernia): almost all patients with reflux esophagitis (esophageal inflammation due to reflux) have such a hernia, but only 10% of all patients with axial hernia show symptoms of reflux esophagitis.
Etiology (Causes)
Biographic causes
- Genetic burden from parents, grandparents
- There are gene variants that are associated with Barrett’s diseases
- Socioeconomic factors – low socioeconomic status.
Behavioral causes
- Nutrition
- Too little fish consumption; inverse correlation between fish consumption and risk of disease.
- Nitrosamine exposure Smoked and cured foods and foods high in nitrates and nitrites Nitrate is a potentially toxic compound: Nitrate is reduced to nitrite in the body by bacteria (saliva/stomach). Nitrite is a reactive oxidant that reacts preferentially with the blood pigment hemoglobin, converting it to methemoglobin. Furthermore, nitrites (also contained in cured sausage and meat products and ripened cheese) form nitrosamines with secondary amines (contained in meat and sausage products, cheese and fish), which have genotoxic and mutagenic effects. The daily intake of nitrate is usually about 70% from the consumption of vegetables (lettuce and lettuce, green, white and Chinese cabbage, kohlrabi, spinach, radish, radish, beet), 20% from drinking water (nitrogen fertilizer) and 10% from meat and meat products and fish.
- Micronutrient deficiency (vital substances) – see prevention with micronutrients; deficiencies of vitamin A, molybdenum and zinc are also believed to have an impact on the development.
- Consumption of stimulants
- Alcohol (esp. concentrated alcohol (≥ 30% by volume)); increases risk of squamous cell carcinoma of the esophagus
- Tobacco (smoking); increases risk for squamous cell carcinoma and adenocarcinoma of the esophagus and esophagogastric junction
- Drug use
- Smoking opiates
- Betel nut (chewing betel nut)/betel nut alkaloids; increases risk for squamous cell carcinoma of the esophagus
- Hot drinks (> 65 °C)
- Psycho-social situation
- High work stress: + 112% esophageal cancer (esophageal cancer).
- Obesity (overweight) – especially the truncal obesity; increases the risk of adenocarcinoma of the esophagus and esophagogastric junction.
- Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)) is presentWhen waist circumference is measured according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
- Men < 94 cm
- Women < 80 cm
The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.
Disease-related causes
- Barrett’s esophagus (synonym: Allison-Johnstone syndrome) – formation of an esophageal peptic ulcer on the metaplastic mucosa; may be a precursor of adenocarcinoma.
- Gastroesophageal reflux disease (synonyms: GERD, gastroesophageal reflux disease; gastroesophageal reflux disease (GERD); gastroesophageal reflux disease (reflux disease); gastroesophageal reflux; reflux esophagitis; reflux disease; reflux esophagitis; peptic esophagitis) – inflammatory disease of the esophagus (esophagitis) caused by the abnormal reflux (reflux) of acidic gastric juices and other gastric contents; increases the risk of adenocarcinoma of the esophagus
- Howel-Evans syndrome (tylosis) – palmo-plantar hypercreatosis/formation of horny calluses on hands and feet; extremely rare disorder of the skin; very high incidence of squamous cell carcinoma of the esophagus (40-100% penetrance)
- Infection with papilloma virus 16 (HPV 16) or Helicobacter pylori.
- Esophageal achalasia – dysfunction of the lower esophageal sphincter (esophageal muscles), with the inability to relax; it is a neurodegenerative disease in which nerve cells of the myenteric plexus die. In the final stage of the disease, the contractility of the esophageal muscles is irreversibly damaged, with the result that food particles are no longer transported into the stomach and lead to pulmonary dysfunction by passing into the trachea (windpipe). Up to 50% of patients suffer from pulmonary (“lung“) dysfunction as a result of chronic microaspiration (ingestion of small amounts of material, e.g., food particles, into the lungs). Typical symptoms of achalasia are: Dysphagia (dysphagia), regurgitation (regurgitation of food), cough, gastroesophageal reflux (reflux of gastric acid into the esophagus), dyspnea (shortness of breath), chest pain (chest pain), and weight loss; as secondary achalasia, it is usually the result of neoplasia (malignant neoplasm), eg. For example, a cardiac carcinoma (stomach entrance cancer); achalasia increases the risk of squamous cell and adenocarcinomas of the esophagus.
- Periodontitis – Detection of Tannerella forsythia in oral flora was associated with a 21% increased risk of adenocarcinoma of the esophagus (EAC); Porphyromonas gingivalis was more common in patients with squamous cell carcinoma of the esophagus (ESCC)
- Plummer-Vinson syndrome (synonyms: sideropenic dysphagia, Paterson-Brown-Kelly syndrome) – symptom complex of trophic disorders (mucosal defects, oral rhagades (tears in the corner of the mouth), brittle nails and hair, burning of the tongue, and dysphagia (difficulty swallowing) caused by major mucosal defects) specifically triggered by iron deficiency. The disease is a risk factor for the development of esophageal cancer.
- Celiac disease (gluten-induced enteropathy) – chronic disease of the mucosa of the small intestine (small intestinal mucosa), which is based on hypersensitivity to the cereal protein gluten; influence on the development of esophageal cancer is not yet clear.
X-rays
- Condition after radiotherapy (radiotherapy) to the cervical-thoracic region; dose-dependent increase in risk of subsequent esophageal cancer.
Environmental exposure – intoxications (poisonings).
