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

• ClinicalTrials.gov Identifier: NCT05105945
• Recruitment Status: Not yet recruiting
• First Posted: November 3, 2021
• Last Update Posted: November 3, 2021
• Sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
• Collaborators: General Hospital of Ningxia Medical University; Beijing Chao Yang Hospital; West China Hospital; Shanghai Chest Hospital; Peking University Cancer Hospital & Institute; The First Affiliated Hospital of Nanchang University; Changzhi Medical College; Zhangzhou Affiliated Hospital of Fujian Medical University; Harbin Medical University; Hubei Cancer Hospital; Jining First People's Hospital; Jiangsu Cancer Institute & Hospital; Nanfang Hospital, Southern Medical University
• Information provided by (Responsible Party): Fifth Affiliated Hospital, Sun Yat-Sen University

Tracking Information

• First Submitted Date: September 16, 2021
• First Posted Date: November 3, 2021
• Last Update Posted Date: November 3, 2021
• Estimated Study Start Date: November 11, 2021
• Estimated Primary Completion Date: December 28, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2021)

• Perioperative incidence of cardiopulmonary complications [ Time Frame: Through operation completion, an average of 12 days ]
  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
• disease-free survival（DFS） [ Time Frame: After surgery-related treatment until the tumor recurrence，assessed up to 5 years ]
  The period after Operation treatment [tumor eliminated] when no disease can be detected
• overall survival（OS） [ Time Frame: 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 ]
  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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 25, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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

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 the"single-port inflatable mediastinoscopy combined with laparoscopy for the radical treatment of esophageal cancer"and 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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant)
Primary Purpose: Treatment

• Condition: Esophageal Cancer

Intervention

• Procedure: Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery
  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.
• Procedure: Thoracoscopy Combined With Laparoscopic Surgery
  Patients will receive a standardized thoracoscopy and laparoscopy combined radical esophageal cancer surgery

Study Arms

• Experimental: Single port inflatable mediastinoscope and synchronized laparoscopic radical resection
  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.
  Intervention: Procedure: Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery
• Active Comparator: Thoracoscopy combined with laparoscopic radical resection
  Patients will receive a standardized thoracoscopy and laparoscopy combined radical esophageal cancer surgery
  Intervention: Procedure: Thoracoscopy Combined With Laparoscopic Surgery

Publications *

• Choi AR, Chon NR, Youn YH, Paik HC, Kim YH, Park H. Esophageal cancer in esophageal diverticula associated with achalasia. Clin Endosc. 2015 Jan;48(1):70-3. doi: 10.5946/ce.2015.48.1.70. Epub 2015 Jan 31.
• Luketich JD, Pennathur A, Franchetti Y, Catalano PJ, Swanson S, Sugarbaker DJ, De Hoyos A, Maddaus MA, Nguyen NT, Benson AB, Fernando HC. Minimally invasive esophagectomy: results of a prospective phase II multicenter trial-the eastern cooperative oncology group (E2202) study. Ann Surg. 2015 Apr;261(4):702-7. doi: 10.1097/SLA.0000000000000993.
• Wang X, Li X, Cheng H, Zhang B, Zhong H, Wang R, Zhong B, Cao Q. 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.
• Fujiwara H, Shiozaki A, Konishi H, Kosuga T, Komatsu S, Ichikawa D, Okamoto K, Otsuji E. Single-Port Mediastinoscopic Lymphadenectomy Along the Left Recurrent Laryngeal Nerve. Ann Thorac Surg. 2015 Sep;100(3):1115-7. doi: 10.1016/j.athoracsur.2015.03.122.
• Fujiwara H, Shiozaki A, Konishi H, Komatsu S, Kubota T, Ichikawa D, Okamoto K, Morimura R, Murayama Y, Kuriu Y, Ikoma H, Nakanishi M, Sakakura C, Otsuji E. Hand-assisted laparoscopic transhiatal esophagectomy with a systematic procedure for en bloc infracarinal lymph node dissection. Dis Esophagus. 2016 Feb-Mar;29(2):131-8. doi: 10.1111/dote.12303. Epub 2014 Dec 9.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 25, 2021): 1164
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 28, 2028
• Estimated Primary Completion Date: December 28, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 18 years old ≤ age ≤ 75 years old, no gender limit;
2. Patients who are diagnosed as esophageal malignant tumor by cytology or histology, and agree to undergo surgical treatment;
3. 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;
4. The tumor is located in the thoracic esophagus;
5. The tumor has not invaded the surrounding vital organs and has metastasized far away;
6. The function of major organs is basically normal: general anesthesia is acceptable for lung function; NYHA grade of heart function is 0~1;
7. 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:

1. People who suffer from other malignant tumors at the same time;
2. Patients with a history of esophagus or gastrectomy;
3. Patients with a history of mediastinal surgery or extensive abdominal cavity adhesion;
4. Patients with basic diseases such as cardiovascular and cerebrovascular diseases;
5. People suffering from mental, mental or neurological diseases;
6. Patients with cachexia and severe malnutrition who cannot tolerate surgery;
7. Recent recurrence of gastric ulcer, history of gastric bleeding and other serious underlying diseases;
8. Patients with surgical contraindications such as blood coagulation dysfunction, HIV antibody positive, and poorly controlled clinically severe infections;
9. 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.
10. Patients who have participated in other clinical studies;
11. Others judged by the investigator to be unsuitable to participate in this clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Cao Qingdong, bachelor; +86 13680356988; 13680356988@163.com

Contact: Wang Xiaojin, master; +86 13798967219; wxjhny@163.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05105945
• Other Study ID Numbers: ZDWY.XXW.005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fifth Affiliated Hospital, Sun Yat-Sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
• Original Study Sponsor: Same as current

Collaborators

• General Hospital of Ningxia Medical University
• Beijing Chao Yang Hospital
• West China Hospital
• Shanghai Chest Hospital
• Peking University Cancer Hospital & Institute
• The First Affiliated Hospital of Nanchang University
• Changzhi Medical College
• Zhangzhou Affiliated Hospital of Fujian Medical University
• Harbin Medical University
• Hubei Cancer Hospital
• Jining First People's Hospital
• Jiangsu Cancer Institute & Hospital
• Nanfang Hospital, Southern Medical University

Investigators

• Study Chair: Liu Shaoxuan; Office of clinical research center

• PRS Account: Fifth Affiliated Hospital, Sun Yat-Sen University
• Verification Date: August 2021