Laparoscopic Proximal Gastrectomy With Double-flap Technique Versus Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction for Proximal Early Gastric Cancer

Laparoscopic Proximal Gastrectomy With Double-flap Technique Versus Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction for Proximal Early Gastric Cancer: a Multi-center Randomized Controlled Trial

Proximal early gastric cancer can choose radical total gastrectomy or proximal gastrectomy. But if use simple esophagogastric anastomosis for proximal gastrectomy, the incidence of postoperative reflux esophagitis is up to 62%, which seriously affects the quality of life, and the short-term outcome is poorer than the total gastrectomy. If the incidence of postoperative reflux esophagitis can be reduced, proximal gastrectomy would be the treatment choice for proximal early gastric cancer, which may more improve both quality of life and nutritional status than total gastrectomy.

Double-flap technique is a new surgical procedure for the reconstruction between esophagus and remnant stomach, which was started to be applied to digestive tract reconstruction in patients with proximal early gastric cancer in 2016. It can reduce the occurrence of reflux oesophagitis. At present, the studies for double-flap technique in China and other countries are mostly retrospective studies, and there are short of large-scale prospective studies and evidence of evidence-based medicine.

The applicant has initiated a phase II, single center, single arm study and the results suggested that the laparoscopic proximal gastrectomy with double-flap reconstruction technique was safe and effective for treating proximal early gastric cancer. To further validate the short and long-term outcomes of this procedure, a multicentre, open label, prospective, superiority and randomised controlled clinical trial was set up to compare laparoscopic proximal gastrectomy with double-flap technique with laparoscopic total gastrectomy with Roux-en-Y reconstruction for proximal early gastric cancer. It include 216 patients with proximal early gastric cancer. The primary outcome is the proportion of patients who develop reflux esophagitis within 12 months after surgery. The short and long-term oncological outcomes are also explored. This trial can provide high-grade evidence of evidence-based medicine for double-flap technique's clinical applications .

Study Overview

• Status: Not yet recruiting
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Procedure: Laparoscopic Proximal Gastrectomy With Double-flap Technique; Procedure: Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Han Fanhai, Professor; Phone Number: +86-135-8031-7677; Email: fh_han@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 20 years ≤ age ≤ 80 years
2. The primary gastric lesions were located in the proximal third of the stomach
3. histologically proven gastric adenocarcinoma (by preoperative gastrofiberscopy)
4. clinical stage IA (T1N0M0) or IB (T1N1M0 / T2N0M0) according to the 8th edition of the American Joint Committee on Cancer(AJCC) staging system(Clinical stage was determined based on the finding of endoscopic ultrasonography and/or thoraco-abdominal contrast-enhanced computed tomography)
5. scheduled for laparoscopic proximal gastrectomy with D1+/D2 lymphadenectomy or laparoscopic total gastrectomy with D1+/D2 lymphadenectomy , and possible for R0 surgery by this procedures (Lymphadenectomy is performed on the basis of the criteria of the Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition).).
6. The preoperative American Society of Anesthesiologists (ASA) physical status was I-III; The patient's cardiopulmonary function can tolerate laparoscopic surgery.
7. The patients have signed the informed consent form.

Exclusion Criteria:

1. history of upper abdominal surgery (except laparoscopic cholecystectomy);
2. the tumor invades the esophagus 3cm above gastro-esophageal junction (Z-line)
3. with other malignant diseases or have suffered from other malignant diseases within 5 years
4. require simultaneous surgery due to complicated with other diseases
5. women are pregnant or in lactation period
6. Suffering from serious mental illness
7. history of continuous systemic corticosteroid or immunosuppressive drug treatment within 1 month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laparoscopic Proximal Gastrectomy With Double-flap Technique	Procedure: Laparoscopic Proximal Gastrectomy With Double-flap Technique; Patients in this group receive laparoscopic proximal gastrectomy with D1+/D2 lymph node dissection(D1+ for stage IA：Nos.1, 2, 3a, 4 sa, 4 sb, 7, 8a, 9, 11p；D2 for stage IB: Nos.1, 2, 3a, 4 sa, 4 sb, 7, 8a, 9, 11p and 11d). The double-flap technique is used for the esophagogastric reconstruction.
Active Comparator: Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction	Procedure: Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction; Patients in this group receive laparoscopic total gastrectomy with D1+/D2 lymph node dissection(D1+ for stage IA：Nos.1, 2, 3, 4, 5, 6, 7, 8a, 9, 11p；D2 for stage IB: Nos.1, 2, 3, 4, 5, 6, 7, 8a, 9, 11p and 11d, 12a). The Roux-en-Y esophagojejunostomy method is used for the esophagojejunal reconstruction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Patients With Reflux Esophagitis Within 12 Months Postoperatively	During follow-up endoscopy 1 year after surgery, reflux esophagitis are graded according to the Los Angeles (LA) classification.	12 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year overall survival rate	3-year overall survival rate	3 years
3-year disease-free survival rate	3-year disease-free survival rate	3 years
3-year recurrence pattern	3-year recurrence pattern	3 years
Quality of Life after Surgery	Quality of life(QoL) is evaluated using the European Organization for Research and Treatment of Cancer (EORTC) 30-item core QoL (QLQ-C30 ver.3.0). Higher scores mean a worse outcome.	Follow-up evaluations are performed 3, 6 and 12 months postoperatively
Gastrointestinal Symptoms after Surgery	gastrointestinal symptoms are assessed by Gastrointestinal Quality of Life Index (GIQLI) questionnaires. Higher scores mean a better outcome.	Follow-up evaluations are performed 3, 6 and 12 months postoperatively
Changes in hemoglobin levels at Follow-up	blood hemoglobin(g/L) levels	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Changes in Vitamin B12 levels at Follow-up	blood Vitamin B12（μg/ml) levels	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Changes in total protein levels at Follow-up	blood total protein(g/L) levels	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Changes in serum albumin levels at Follow-up	blood serum albumin(g/L) levels	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Changes in prealbumin levels at Follow-up	blood prealbumin(g/L) levels	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Late Postoperative Morbidity	adhesive ileus, anastomosis stenosis, malnutrition, dumping syndrome. All postoperative complications are classified according to the Clavien-Dindo(CD) classification standard.	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Early Postoperative Morbidity	operation wound with seroma, hematoma, infection, dehiscence, or evisceration, anastomotic leakage, anastomotic bleeding, abdominal bleeding, abdominal abscess, intestinal obstruction morbidity, gastrointestinal bleeding, gastroparesis, postoperative pancreatitis, pancreatic fistula, chylous leakage, lung morbidity, cerebrovascular morbidity, cardiovascular morbidity, deep vein thrombosis, cholecystitis, liver dysfunction, kidney dysfunction. All postoperative complications are classified according to the Clavien-Dindo(CD) classification standard.	From surgery to discharge, up to 30 days
Short-term Clinical Outcome After Surgery	time to pass gas(hours)	From surgery to discharge, up to 30 days
Short-term Clinical Outcome After Surgery	time to oral intake(hours)	From surgery to discharge, up to 30 days
Short-term Clinical Outcome After Surgery	time to indwell gastric tube(hours)	From surgery to discharge, up to 30 days
Short-term Clinical Outcome After Surgery	length of postoperative hospitalisation(days)	From surgery to discharge, up to 30 days
Surgical Characteristics	operative time(minutes)	24 hours postoperatively
Surgical Characteristics	time for reconstruction the digestive tract(minutes) during surgery	24 hours postoperatively
Surgical Characteristics	blood loss(ml) during surgery	24 hours postoperatively
5-year disease-free survival rate	5-year disease-free survival rate	5 years
5-year overall survival rate	5-year overall survival rate	5 years
5-year recurrence pattern	5-year recurrence pattern	5 years
body mass index postoperatively	body mass index(kg/m^2)	Follow-up evaluations are performed 3, 6 and 12 months postoperatively.
Quality of Life postoperatively	Quality of life(QoL) is evaluated using the European Organization for Research and Treatment of Cancer (EORTC) gastric cancer module (QLQ-STO22) questionnaire. Higher scores mean a worse outcome.	Follow-up evaluations are performed 3, 6 and 12 months postoperatively
Postoperative pain assessment	We measured the pain score using visual analog scale(VAS) at 24 hours after the surgery is completed. Higher scores mean a worse outcome.	Day 1 postoperatively
Pathological Characteristics	lymph nodes dissection extent for each patient in the surgery	1 week postoperatively
Pathological Characteristics	number of dissected lymph nodes for each patient in the surgery	1 week postoperatively
Pathological Characteristics	R0 resection rate. R0 resection represents complete resection of the tumor, meaning there is no residual tumor.	1 week postoperatively
Proportion of participants die after surgery	mortality rate	From surgery to discharge, up to 30 days
Proportion of participants need to rehospitalized after surgery	rehospitalization rate.	From surgery to discharge, up to 30 days

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: LanZhou University; Qilu Hospital of Shandong University; Tianjin Medical University Cancer Institute and Hospital; The First Affiliated Hospital of Zhengzhou University; Gansu Provincial Hospital; Third Affiliated Hospital, Sun Yat-Sen University; First Hospital of China Medical University; Shandong Provincial Hospital Affiliated to Shandong First Medical University; Sichuan Provincial People's Hospital; Liaoning Tumor Hospital & Institute; Sichuan Cancer Hospital and Research Institute; Zunyi Medical College; First Affiliated Hospital of Guangxi Medical University; First Affiliated Hospital of Kunming Medical University; Qinghai Province Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2023
• Primary Completion (Estimated): December 10, 2029
• Study Completion (Estimated): May 10, 2033

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 26, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: laparoscopy; Gastrectomy; Reflux Esophagitis; minimally invasive surgical procedures; stomach neoplasm
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: SYSKY-2022-276-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No