Background :
Esophageal carcinoma is an aggressive disease with a poor prognosis. Surgical resection with radical lymphadenectomy remains the basic method of management of this malignancy. The international Society for Diseases of the Esophagus has classified the extent of lymphadenectomy as standard, extended, total, and three-field lymphadenectomy. However, lymph node metastases can be present as regional metastasis, skip metastasis and distant metastasis, the optimal extent of lymphadenectomy remains controversial by now. Three-filed lymphadenectomy was criticized for higher surgical risks, but have the merits of removing all potential positive nodes and reducing the local recurrence. The purpose of this study is to conduct a large scale prospective randomized Phase Ⅲ clinical trial to test that based on the long-term outcomes(overall survival and disease free survival )and postoperative short-term outcomes(mortality, morbidity),whether one extent of lymphadenectomy is superior than the other approach or not.
Objectives:
1. To compare overall survival after three-field lymphadenectomy and two-field lymphadenectomy
2. To compare locoregional recurrence, disease free survival after three-field lymphadenectomy and two-field lymphadenectomy
3. To compare postoperative morbidity and mortality in the two groups
Design: Prospective randomized controlled Setting: Fudan University Cancer Center, Shanghai, China. Patients and methods : All patients with biopsy proven carcinoma of the middle or lower third of the esophagus presenting to our hospital will be considered for the study.
Staging investigations will be standard and will include
1. Computed Tomography (CT) scans in all patients
2. Esophagogastroscopy
3. Barium swallow
4. Endoscopic Ultrasonography (EUS) wherever possible
5. PET-CT scan wherever possible
Randomization:
Randomization, by the sealed envelope method, took place on the morning of planed surgery day.
All surgeries will be performed under general anesthesia with epidural analgesia. The surgery will be either performed by or under the direct supervision of consultant thoracic surgeons with experience in esophageal surgery. Operative time, blood loss, blood product replacement and all intraoperative details will be recorded in the proforma. Patients will be shifted postoperatively to the intensive care unit (ICU) for observation and subsequently to the recovery or high dependency ward once stabilized. Postoperative details including period of postoperative ventilation, hemorrhage, pulmonary and cardiac complications, arrhythmias, thoracic duct leak, anastomotic leak, wound infection and recurrent laryngeal nerve paresis or palsy will be recorded. Postoperative mortality will be defined as 30-day mortality plus death before discharge after surgery. The total duration of ICU stay and hospital stay will also be recorded.
Follow up:
Patients will be followed up three monthly for the first two years and six monthly for the third to fifth years and annually thereafter. A detailed history and clinical examination and CT scan, barium swallow and ultrasound will be done routinely on every follow up.
Data management: All collected data will be entered into a statistical software package for subsequent analysis
Main research variables:
Primary end point: Overall survival
Secondary endpoints:
1. Disease free survival in the two arms
2. Locoregional recurrence
3. Postoperative morbidity and mortality
