Laparoscopic Versus Open Lower Mediastinal Lymphadenectomy for Esophagogastric Junction Cancer

Study Overview
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Brief Summary
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Mediastinal lymph node dissection has been adopted as standard treatment for adenocarcinoma of esophagogastric junction(AEJ). This multi-center, exploratory, prospective, cohort study aims at provide standard technical details of laparoscopic mediastinal lymph node dissection, and explore the potential clinical effects, gather key information for following study regarding sample size calculation, primary outcome and feasibility.

Detailed Description
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Introduction: Lower mediastinal lymph node dissection has been adopted as standard by treatment guideline for adenocarcinoma of esophagogastric junction(AEJ), but the effect of laparoscopic mediastinal lymph node dissection remains unknown. The aim of this study is to provide standard technical details of laparoscopic mediastinal lymph node dissection, and explore the potential clinical effects, gather key information for following study regarding sample size calculation, primary outcome and feasibility. This study report intervention development, governance procedures and selection and reporting of outcomes to optimize methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice. Methods and analysis: This is an IDEAL stage II, prospective, parallel control, open label, multi-center and exploratory study. The inclusion criteria is Siewert II/ III, AEJ, cT2-4aN0-3M0(AJCC-8th Gastric Cancer TNM stage manual), decide to receive radical gastrectomy, without preoperative anti-neoplastic therapy. The individual included in the study is performed the radical total or proximal gastrectomy plus the lower mediastinal lymphadenectomy via either laparoscopic (trial arm) or open (control arm) TH approach. The surgical approach is determined by the investigator in each center before the operation and recorded in the electronic case report forms (CRF). The primary outcome is the number of lower mediastinal lymph nodes retrieved. Secondary outcome include complication, surgery length, postoperative death, R0 resection rate, etc. Expected sample size is 518 in each group, thus has 80% power to detect a difference of 0.17 in the average number of lower mediastinal lymph node dissected in between two groups.

Official Title
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Laparoscopic Versus Open Lower Mediastinal Lymphadenectomy for Siewert Type II/III Adenocarcinoma of Esophagogastric Junction: an Exploratory, Prospective, Observational, IDEAL Stage 2, Cohort Study

Conditions
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Gastric Cancer

Intervention / Treatment
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* Procedure: Radical gastrectomy with dissection of lower mediastinal lymph node


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years old; Karnofsky score ≥70%;Or ECOG score ≤2; Preoperative pathological biopsy confirmed adenocarcinoma. According to gastroscopy, abdominal CT or upper gastrointestinal angiography, the tumor site conforms to the definition of esophageal and gastric junction adenocarcinoma in the Chinese expert consensus, that is, the tumor center is within 5cm above and below the esophagogastric anatomical junction and crosses or touches the esophagogastric junction; Length of esophageal invasion ≤2cm; By abdominal contrast-enhanced CT/MRI, the clinical stage was CT2-4aN0-3M0 (according to AJCC-8th TNM tumor stage); Subject's blood routine and biochemical indicators meet the following standards: hemoglobin ≥80g/L; Absolute count of neutrophils (ANC) ≥1.5×109/L; Platelet ≥75×109/L;ALT and AST≤2.5 times the normal upper limit; ALP≤2.5 times the normal upper limit; Serum total bilirubin ≤1.5 times the normal upper limit; Serum creatinine ≤ the normal upper limit; Serum albumin ≥30g/L; Obtain written informed consent. Exclusion Criteria: Any anti-cancerous treatment received prior to surgery. Multiple malignant lesions in the stomach. Suspicious lymph node metastasis in the middle and/or upper mediastinum. Surgical history in the upper abdomen (laparoscopic cholecystectomy excluded). Pregnant or breastfeeding women. Uncontrolled epilepsy, central nervous system disease or mental disorder. The Bulky N2 status. The emergency surgery. Severe heart disease. History of cerebral infarction or cerebral hemorrhage within 6 months. Organ transplant recipients who need immunosuppressive therapies. Other malignancy diagnosed within 5 years (cured dermoid caner and cervical cancer excluded).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Laparoscopic Surgery<br>Lower Mediastinal Lymphadenectomy should be finished via laparoscopic method. | Procedure: Radical gastrectomy with dissection of lower mediastinal lymph node<br>* Radical gastrectomy for gastric cancer should be consistent with Japanese gastric cancer treatment guideline.<br>|
| Open Surgery<br>Lower Mediastinal Lymphadenectomy should be finished via open method. | Procedure: Radical gastrectomy with dissection of lower mediastinal lymph node<br>* Radical gastrectomy for gastric cancer should be consistent with Japanese gastric cancer treatment guideline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of lower mediastinal lymph nodes retrieved | The number of lower mediastinal lymph nodes retrieved | immediately after the pathology report issued | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complication during Lower Mediastinal Lymphadenectomy | Complication during Lower Mediastinal Lymphadenectomy & anastomosis, including damage of pericardium, esophagus, etc. | immediately after the surgery | 
| Rate of postoperative complication after Lower Mediastinal Lymphadenectomy | Postoperative complication after Lower Mediastinal Lymphadenectomy, including leakage, bleeding, etc, complication related with Lower Mediastinal Lymphadenectomy | Day 30 after surgery | 
| Time length of Lower Mediastinal Lymphadenectomy | Time length of Lower Mediastinal Lymphadenectomy | immediately after the surgery | 
| Rate of Postoperative complication | Any complication within 30d after surgery | Day 30 after surgery | 
| Rate of postoperative death | death within 30 days after surgery | Day 30 after surgery | 
| Rate of unscheduled reoperation | reoperation within 30 days after surgery | Day 30 after surgery | 
| Rate of unscheduled readmission | unscheduled readmission within 30 days after surgery | Day 30 after surgery | 
| R0 resection rate | R0 resection rate | immediately after the pathology report issued | 
| Proximal margin length | from proximal tumor margin to proximal margin | 30minutes after removal of tumor | 
| Local recurrence of lower mediastinal area in 3 years | Local recurrence of lower mediastinal area in 3 years | Year 3 after surgery | 
| Rate of cancer specific death in 3 years | Rate of cancer specific death in 3 years | Year 3 after surgery | 
| Recurrence free survival in 3 years | Recurrence free survival in 3 years | Year 3 after surgery | 
| Overall survival in 3 years | Overall survival in 3 years | Year 3 after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophagogastric junction, lower mediastinal lymphadenectomy, laparoscopic gastrectomy, IDEAL framework