Esophageal cancer SCC Adenocarcinoma SCC and adenocarcinoma :more than 95 percent of esophageal malignant tumors.

Epidemiology AC is largely a disease of Caucasians and males, who outnumber females by as much as 6-8to 1 . incidence of esophageal AC in Caucasian males was 4.2 per 100,000 per year, double that of Hispanics and four-fold higher than those of blacks and Asians . SCC incidence rates were highest in blacks (8.8 per 100,000 per year), and Asians (3.9 per 100,000 per year)

Esophagus/cancer early/advanced Early esophageal cancer may appear as a superficial plaque or ulceration .

Esophagus/cancer

Esophagus/cancer Advanced/gross features Advanced lesions may appear as a stricture an ulcerated mass ,a circumferential mass or a large ulceration.

Esophagus/cancer

Esophagus/cancer

Esophagus/cancer

Esophagus/cancer SCC/major risk factors Smoking and alcohol are major predisposing factors for squamous cell tumors.

Esophagus/cancer Risk factors history of smoking, alcohol consumption, diets low in fruits and vegetables accounted for almost 90 percent of esophageal squamous cell carcinoma in the United States.

Esophagus/cancer Adenocarcinoma/risk factors Barrett's esophagus with specialized intestinal metaplasia and possibly GERD itself are the only known major risk factors for adenocarcinoma.

Barrett’s esophagus

Esophageal adenocarcinoma with barrett’s esophagus

Epidemiology the incidence of SCC is decreasing in the United States, the incidence of adenocarcinoma (AC) is rising dramatically. The prognosis for both types of cancer is poor. Five-year survival is 10 to 13 percent, patients diagnosed with early stage disease may be cured by surgery or multimodality therapy.

Esophagus/cancer Epidemiology Squamous cell carcinoma incidence : varies among geographic regions The highest rates : Asia (particularly in China and Singapore), Africa, and Iran . Geographic variation has also been reported within an individual country. Within China, rates of esophageal cancer range from 1.4 to 140 per 100,000 in the Hebi and Hunyuan counties, respectively .

Demographic and socioeconomic factors/SCC  Wide difference in the rates of SCC have provided insight into risk factors associated with the disease. In high incidence regions, the disease has no gender specificity. SCC is more common in men in low incidence regions. The incidence is higher in urban areas (compared to rural areas) of the United States, particularly among African-American men. Lower socioeconomic status was associated with esophageal SCC in a large population-based study.

Risk factors for SCC Smoking and alcohol are also risk factors for head and neck cancers, which are found in approximately 10 to 15 percent of patients diagnosed with esophageal cancer.

Risk factors for SCC Dietary factors  Foods containing N-nitroso compounds have long been implicated Certain types of pickled vegetables and other food-products consumed in high-risk endemic areas are rich in N-nitroso compounds Toxin-producing fungi have also been identified in food sources within endemic areas and may, in part, exert their mutagenic potential by reducing nitrates to nitroso compounds. Betel nut chewing, which is widespread in certain regions of Asia, has been implicated in the development of esophageal SCC .The mechanism may involve the release of copper with resulting induction of collagen synthesis by fibroblasts.

Risk factors for SCC In other endemic regions, such as Iran, Russia, and South Africa, ingestion of very hot foods and beverages (such as tea) has been associated with esophageal SCC. In one epidemiologic study, significantly more people in high-risk regions within Iran drank their tea at temperatures greater than 65ºC compared to low-risk regions (62 versus 19 percent) inhabitants of high-risk regions drank approximately 2.5 times more hot tea than their low-risk counterparts.

Protective factors for SCC Low levels of serum selenium were associated with the development of squamous cell cancer of the esophagus and gastric cardia cancer in a study from Linxian, China . selenium supplementation may be associated with a reduced risk of these cancers zinc deficiency and esophageal squamous cell cancer.

Protective factors for SCC potential mechanisms : Zinc deficiency enhances the carcinogenic effects of nitrosamines in rat models of esophageal carcinogenesis zinc appears to reduce overexpression of COX-2, which is thought to contribute to carcinogenesis by enhancing cellular proliferation, inhibition of apoptosis, and increasing metastatic potential increased dietary folate :reduced risk of squamous cell and adenocarcinoma of the esophagus   

Risk factors for SCC Underlying esophageal disease Achalasia : the risk of SCC was increased more than 16-fold. cancer was detected an average of 14 years after the diagnosis of achalasia caustic strictures: SCC developed 41 years following ingestion. Patients who have undergone a partial gastrectomy also may be at increased risk?

Risk factors for SCC Human papilloma virus Tylosis (hyperkeratosis of the palms of the hands and soles of the feet, autosomal dominant to chromosome 17q25.1, which probably contains a tumor suppressor gene. Deletions in this gene have also been implicated in sporadic forms of esophageal SCC, occurring in 70 percent of patients with esophageal SCC in one series).

Risk factors for SCC Upper aerodigestive tract cancer history of squamous cell cancer of the head and neck (ie, oral cavity, oropharynx, hypopharynx, or larynx), lung or esophagus with synchronous or metachronous squamous cell carcinoma of the esophagus This probably reflects similar risk factors such as smoking or alcohol. the incidence of synchronous or metachronous esophageal cancer has range from 3 to 14 percent

Adenocarcinoma Epidemiology In the 1960s, SCC accounted for >90 % of all esophageal tumors in the United States, whereas AC were considered so uncommon that some authorities questioned their existence. For the past three decades, the frequency of AC of the esophagus and the gastric cardia has increased dramatically in Western countries. SCC and AC now occur with almost equal frequency incidence rates of esophageal AC rose progressively from 1.8 per 100,000 in 1987 to 1991 to 2.5 per 100,000 during 1992 to 1996. Whites were affected five times more often than blacks, and men six-eight times more often than women. A significant increase in the incidence was observed among persons aged 45 to 65.

Adenocarcinoma Risk factors Gastroesophageal reflux disease Esophageal adenocarcinoma arises from Barrett's metaplasia. The role of chronic reflux as an independent risk factor has not been well defined since more than 50 % of cases of AC have no history of symptomatic reflux disease . Reflux symptoms were associated with adenocarcinoma of the esophagus (odds ratio 7.7) The risk was greatest among patients with long-standing (>20 years) and severe (as judged by the patient) symptoms (odds ratio 43.5).

Adenocarcinoma Risk factors Smoking : Smoking probably increases the risk of AC, particularly in patients with Barrett's esophagus.the risk of AC was 2.4 times greater in smokers than a control group, and accounted for 40 percent of the cases of esophageal AC . The risk rose with increasing intensity and duration of smoking, and remained higher than in nonsmoking controls for 30 years after smoking cessation.  Obesity : Obesity has been linked to esophageal AC.

Adenocarcinoma Risk factors  Helicobacter pylori infection.  Increased esophageal acid exposure .   Use of drugs that decrease lower esophageal sphincter pressure.  Cholecystectomy Nitrosative stress

Adenocarcinoma Protective factors Possible protective effect of cereal fiber and other nutrients Possible protective effect of NSAIDs

Esophagus/cancer Signs & symptoms Early symptoms :subtle and nonspecific. Transient "sticking" of apples, meat, hard-boiled eggs, or bread, which can be easily overcome by the patient with careful chewing, may precede frank dysphagia. retrosternal discomfort or a burning sensation. Most early esophageal cancer in the United States is detected serendipitously or during screening of Barrett's esophagus.

Esophagus/cancer Signs & symptoms Regurgitation of saliva or food uncontaminated by gastric secretions (advanced disease). Aspiration pneumonia ( infrequent). Hoarseness (recurrent laryngeal nerve).

Esophagus/cancer Signs & symptoms Chronic gastrointestinal blood loss (common,IDA) . melena or blood in regurgitated food(rare). acute upper gastrointestinal bleeding (rare ,tumor erosion into the aorta or pulmonary or bronchial arteries).

Esophagus/cancer Signs & symptoms Tracheobronchial fistulas ( late). intractable coughing or frequent pneumonias. Life expectancy is less than four weeks following the development of this complication.

Esophagus/cancer Clinical manifestations Both AC and SCC have similar clinical presentations. AC arises much more commonly in the distal esophagus. progressive solid food dysphagia( lumen diameter is less than 13 mm) which indicates advanced disease. weight loss(due to dysphagia, changes in diet, and tumor anorexia).

Esophagus/cancer Diagnostic tests: barium studies endoscopy .

Esophagus/cancer Staging CT scan: to evaluate for the presence of metastatic disease. If negative:EUS

Esophagus/cancer EUS

Esophagus/cancer treatment Surgery Chemoradiation Palliative

Esophagus/cancer Palliative Rx Endoscopic interventions for palliation of dysphagia in the following settings: Patients for whom definitive management with radiation or chemoradiotherapy is planned, but who have severe dysphagia at presentation, requiring intervention prior to therapy.

Esophagus/cancer Palliative Rx Failure to achieve adequate palliation of dysphagia with initial therapy. Recurrent dysphagia due to locoregional failure Recurrent. dysphagia due to benign strictures in patients who are successfully treated with radiation. Patients are poor candidates for either chemotherapy or radiation therapy.

Esophagus/cancer Endoscopic approaches : Dilation Laser therapy Endoscopic injection therapies Endoscopic mucosal resection Photodynamic therapy Placement of prosthetic tubes (stenting) Brachytherapy

Examples of self-expandable esophageal stents

Esophagus/cancer others tumor Mesenchymal tumors commonly found in the mid to distal third of the esophagus. usually small and asymptomatic dysphagia.

Esophagus/ others tumor leiomyoma More common more common in men detected incidentally on a barium swallow or endoscopy performed for other reasons In endoscopy: rounded submucosal lesions with intact overlying mucosa, and feel rubbery when gently palpated with the endoscope. Ulceration or bleeding (uncommon).

Esophagus/leiomyoma

Esophagus/leiomyoma Follow-up studies :repeat endoscopy and EUS at 6 and 12 months. Surgical resection: lesions larger than 2 cm or if produce dysphagia.