Clinical Study on the Efficacy of Single-port Inflatable Mediastinoscopy Combined With Laparoscopic-assisted Small Incision Surgery and Thoracoscopy Combined With Laparoscopic Surgery for Radical Esophagectomy

Study Overview
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Brief Summary
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We previously developed a novel non-trans thoracic esophagectomy, the single-port inflatable mediastinoscopy combined with laparoscopy for the radical esophagectomy of esophageal cancer.This study is evaluating the feasibility and safety of radical resection of single-port inflatable mediastinal mirror synchronization with laparoscopic esophageal carcinoma, as well as the clinical value of the radical resection of single-port inflatable mediastinal mirror synchronization with laparoscopic esophageal carcinoma as a new minimally invasive operation for esophageal carcinoma.

Detailed Description
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To reduce postoperative pulmonary complications, considerable efforts have been made to develop the nontransthoracic esophagectomy for esophageal cancer. For instance, esophageal stripping and transhiatal esophagectomy are the nontransthoracic operations developed for treatment for esophageal cancer. These methods possess several advantages, including non-thoracotomy, less postoperative pain, less postoperative cardiac and pulmonary complications, and safer for elderly patients. However, these two methods are limited with the poor surgical view, poor mediastinal lymph node dissection (especially upper mediastinal lymph nodes), and high risk of bleeding. In 2015 and 2016, Prof. Fujiwara has developed novel surgical methods on the dissection of upper mediastinal lymph nodes using single-port mediastinoscopy through the cervical incision and the lower mediastinal lymph nodes (including the subcarinal lymph nodes) by laparoscopy, respectively.For the first time, non-transthoracic radical resection of esophageal cancer could be achieved along with the dissection of all the mediastinal lymph nodes. Based on the Fujiwara's method, we further improved this surgical method to thesingle-port inflatable mediastinoscopy combined with laparoscopy for the radical treatment of esophageal cancerand has successfully performed this novel surgical method for the first case in March 2016. We have completed over 200 cases of radical resection of esophageal carcinoma using this novel surgical technique from May 2016 to August 2021. This is a prospective, multicenter, open clinical study in which 1164 patients (including 10% drop-off rate) who require surgical treatment are scheduled to be included in the study. Prior to any screening process, each subject / legal guardian should sign the informed consent form. Screening tests are used to determine whether each subject is eligible for the study. Eligible subjects who meet the standard will be treated with radical resection of single-hole inflatable mediastinal mirror synchronization with laparoscopic esophageal carcinoma and followed up until 5 years postoperatively. Primary study outcome are the prioperative complication rate and the number of intraoperative lymph node dissection.

Official Title
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A Randomized, Controlled, Multi-center Clinical Study on the Efficacy of Single-port Inflatable Mediastinoscopy Combined With Laparoscopic-assisted Small Incision Surgery and Thoracoscopy Combined With Laparoscopic Surgery for Radical Esophagectomy

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Procedure: Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery
* Procedure: Thoracoscopy Combined With Laparoscopic Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old ≤ age ≤ 75 years old, no gender limit; Patients who are diagnosed as esophageal malignant tumor by cytology or histology, and agree to undergo surgical treatment; The preoperative clinical tumor staging is T1-2N0-1M0 patients; or T3N1-2M0 patients undergo neoadjuvant treatment (neoadjuvant chemotherapy, neoadjuvant chemoradiation, neoadjuvant radiotherapy, neoadjuvant chemotherapy and immunotherapy, neoadjuvant radiotherapy and immunotherapy After treatment), assess the tumor to achieve partial response (PR) and surgical resection is feasible; The tumor is located in the thoracic esophagus; The tumor has not invaded the surrounding vital organs and has metastasized far away; The function of major organs is basically normal: general anesthesia is acceptable for lung function; NYHA grade of heart function is 0 1; Voluntarily sign an informed consent form before the study. The patient and/or his legal representative have the ability to fully understand the content, process and possible adverse reactions of the experiment, and enable the patient to comply with the visits stipulated in the plan; Exclusion Criteria: People who suffer from other malignant tumors at the same time; Patients with a history of esophagus or gastrectomy; Patients with a history of mediastinal surgery or extensive abdominal cavity adhesion; Patients with basic diseases such as cardiovascular and cerebrovascular diseases; People suffering from mental, mental or neurological diseases; Patients with cachexia and severe malnutrition who cannot tolerate surgery; Recent recurrence of gastric ulcer, history of gastric bleeding and other serious underlying diseases; Patients with surgical contraindications such as blood coagulation dysfunction, HIV antibody positive, and poorly controlled clinically severe infections; Patients with other comorbid diseases (such as liver and kidney function abnormalities, etc.) or concomitant medications, which may have an impact on the results of this study based on the judgment of the investigator. Patients who have participated in other clinical studies; Others judged by the investigator to be unsuitable to participate in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The Logrank method was used to compare the difference in survival time between the two groups of patients. According to previous literature data, it is estimated that the DFS of the control group is 18 months. Assuming that the DFS of the test group can be extended to 21.6 months (corresponding HR=1.20), the test requires 1048 patients (524 in each group) to achieve α=0.05 This difference can be detected with 80% confidence at the (two-sided) significance level. The trial plans to enroll for 48 months, follow up for 60 months, and conduct a final analysis when 944 patients have tumor progression (recurrence or metastasis). It is estimated that the drop-off rate of patients in the experimental group and the control group is 10%, so 1164 (524×2÷0.9=1164) patients need to be enrolled in the final group. Significance Level：0.05
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single port inflatable mediastinoscope and synchronized laparoscopic radical resection<br>Detailed surgical procedures and related instructions have been published in Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery for Radical Esophagectomy Is an Effective and Safe Treatment for Esophageal Cancer J Gastrointest Surg. 2019 Aug;23(8):1533-1540. doi: 10.1007/s11605-018-04069-w. Epub 2019 Jan 11. | Procedure: Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery<br>* Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery dissects, dissociates and removes the esophagus in the mediastinum through an inflatable endoscopy. Detailed surgical procedures and related instructions have been published in Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery for Radical Esophagectomy Is an Effective and Safe Treatment for Esophageal Cancer J Gastrointest Surg. 2019 Aug;23(8):1533-1540. doi: 10.1007/s11605-018-04069-w. Epub 2019 Jan 11.<br>|
| Active Comparator: Thoracoscopy combined with laparoscopic radical resection<br>Patients will receive a standardized thoracoscopy and laparoscopy combined radical esophageal cancer surgery | Procedure: Thoracoscopy Combined With Laparoscopic Surgery<br>* Patients will receive a standardized thoracoscopy and laparoscopy combined radical esophageal cancer surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative incidence of cardiopulmonary complications | Perioperative complications include: pulmonary infection, respiratory failure, managed pleural effusion, heart failure, myocardial infarction, managed arrhythmia, anastomotic fistula or gastric fistula, recurrent laryngeal nerve injury, chylothorax, unscheduled reoperation | Through operation completion, an average of 12 days | 
| disease-free survival（DFS） | The period after Operation treatment [tumor eliminated] when no disease can be detected | After surgery-related treatment until the tumor recurrence，assessed up to 5 years | 
| overall survival（OS） | When the precise cause of Esophageal cancer death is not specified, this is called the overall survival rate or observed survival rate. Doctors use mean overall survival rates to estimate the patient's prognosis. This is often expressed over standard time periods, like one, five, and ten years. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intraoperative blood loss | Calculation of intraoperative bleeding with ml/kg | During the operation, an average of 2 hours | 
| Operation time | Calculate the operating time in minutes | During the operation, an average of 2 hours | 
| Proportion of patients who converted to thoracotomy and laparotomy | The ratio of the number of patients converted to thoracotomy or laparotomy to the total number of patients undergoing surgery | During the operation, an average of 2 hours | 
| Intraoperative mortality rate | The ratio of the number of patients who died during the operation to the number of patients who underwent the operation | During the operation, an average of 2 hours | 
| Postoperative hospital stay | The days of postoperative hospitalization | Through postoperative hospital stay, an average of 4 days | 
| Postoperative pain score | Daily pain scores were recorded by VAS (Visual Analogue Scale/Score) 1-3 days after operation | An average of 3 days after the operation | 
| Postoperative admission time to ICU | If the patient needs to be transferred to ICU after operation, stay in icu monitoring time should be observed | An average of 3 days after the operation | 
| Postoperative drainage | Total postoperative thoracic or mediastinal drainage (ml/kg) | An average of 3 days after the operation | 
| Postoperative retention time of various types of drainage tubes | The retention time of different types of drainage tube | An average of 3 days after the operation | 
| Number of lymph nodes removed during surgery | The number of dissected lymph nodes reported in the postoperative pathology report | Pathology report time, an average of 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Minimally invasive surgery