**1. Introduction**

Esophageal cancer is the eighth most common cancer worldwide, besides being the sixth most common cause of cancer death. There were 456,000 new cases in the world in 2012 [1]. It is four times more common in men than in women; it occurs more frequently among people above 45 years of age and reaches its plateau among people at 65–74 years of age. Its mortality is high; it can be as high as 84%. For the locally advanced disease, the 5-year survival

is 15–34%. The cornerstone of treatment remains surgery; however, there is evidence that survival is favorably influenced when additional therapies, such as chemotherapy or radiation therapy or their combination, or targeted therapies are used for lymph node-positive or cT2 or tumors that are larger than cT2. The clinical studies assessing treatment modalities for esophageal cancer are diverse: the modalities (chemotherapy, radiation therapy and surgery) have been evaluated in various orders and combinations. The number of study subjects has rarely been over 100 per study. The study populations have not always been homogeneous; different portions of the esophagus were affected, and the study population is sometimes mixed, regarding staging and histology.

#### **1.1. Histology**

Histology is usually based on the histologic analysis of an endoscopic sample. There are two main types of esophageal cancer: squamous cell carcinoma (SCC) and adenocarcinoma. Squamous cell carcinoma mostly occurs in the lining in the upper portion of the esophagus. Adenocarcinoma develops at the junction between the esophagus and the stomach. Most of the tumors are squamous cell carcinoma, but the incidence of adenocarcinoma has been increasing.

#### **1.2. Predisposing factors**

Intraepithelial neoplasias, such as epithelial dysplasias and in situ carcinoma, are the most significant precursor lesions for the development of esophageal cancer. Generally, it occurs a decade prior to carcinoma. The classification of dysplasias is based on the extent of the epithelial involvement. Some of the dysplasias show spontaneous regression. Nearly 30% of the severe dysplasias become invasive cancer. Tobacco use and/or consuming alcohol predominantly increase the risk of esophageal squamous cell carcinoma. Being overweight and/or reflux disease can primarily increase the risk of esophageal adenocarcinoma.

The multifocal appearance and intramural spread are common characteristics of esophageal cancer. It often spreads through the lymphatic system. Tumors involving the proximal portion of the esophagus may give metastases to the cervical lymph nodes, and tumors involving the lower portion may also give metastasis to the vicinity of the celiac artery. Cancer can infiltrate its surroundings, the pars membranacea of the trachea and the prevertebral fascia.
