Summary Anastomotic leakage is one of the most severe complications after esophagectomy and is associated with increased postoperative morbidity and mortality. Several projects ranging from small retrospective studies to large collaborations have aimed to identify potential pre- and perioperative risk factors and to improve the diagnostic processes and management. Despite the increase in available literature, many aspects of anastomotic leakage are still debated, without the existence of widely accepted guidelines. The purpose of this review is to provide a cutting edge overview of the recent literature regarding the definition and classification of anastomotic leakage, risk factors, novel diagnostic modalities, and emerging therapeutic options for treatment and prevention of anastomotic leakage following esophagectomy.

Background An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. Methods The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. Discussion The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. Trial registration NCT03222895 , date of registration: July 19th, 2017.

The incidence of esophageal cancer increases, with approximately 482,000 patients diagnosed with esophageal cancer each year. Despite the growing incidence of esophageal carcinoma, the extent of the lymphadenectomy is still under discussion. Lymph node status is an important prognostic parameter in esophageal cancer and an independent predictor of survival. Surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy differs worldwide. For squamous cell cancer, Japanese surgeons have standardized the 2-or 3-field lymphadenectomy according to the location of the tumor. For adenocarcinoma, in the Western World accounting for 85% of all esophageal cancers, the type of lymphadenectomy to perform is not clear. Moreover, the use of neoadjuvant therapy may influence the mediastinal lymph nodes and the significance of the lymphadenectomy for survival. These aspects have challenged the traditional policy concerning lymphadenectomy, at least in the Western World. Furthermore, an extensive lymphadenectomy may improve survival but, on the other hand, may cause significant more morbidity. An overview of the literature on the extent of lymphadenectomy for esophageal cancer with respect to the supposed lymph node distribution patterns for squamous cell carcinoma and adenocarcinoma, the different lymph node classification systems, the commonly used surgical techniques and outcomes, and the proposal of observational cohort study to standardize the type of lymphadenectomy according to the type of tumor, location and use of neoadjuvant therapy will be provided.