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

Study Overview
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Brief Summary
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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 .

Official Title
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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

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Procedure: Laparoscopic Proximal Gastrectomy With Double-flap Technique
* Procedure: Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 years ≤ age ≤ 80 years The primary gastric lesions were located in the proximal third of the stomach histologically proven gastric adenocarcinoma (by preoperative gastrofiberscopy) 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) 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).). The preoperative American Society of Anesthesiologists (ASA) physical status was I-III; The patient's cardiopulmonary function can tolerate laparoscopic surgery. The patients have signed the informed consent form. Exclusion Criteria: history of upper abdominal surgery (except laparoscopic cholecystectomy); the tumor invades the esophagus 3cm above gastro-esophageal junction (Z-line) with other malignant diseases or have suffered from other malignant diseases within 5 years require simultaneous surgery due to complicated with other diseases women are pregnant or in lactation period Suffering from serious mental illness history of continuous systemic corticosteroid or immunosuppressive drug treatment within 1 month

Ages Eligible for Study
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Minimum Age: 20 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laparoscopic Proximal Gastrectomy With Double-flap Technique<br> | Procedure: Laparoscopic Proximal Gastrectomy With Double-flap Technique<br>* 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.<br>|
| Active Comparator: Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction<br> | Procedure: Laparoscopic Total Gastrectomy With Roux-en-Y Reconstruction<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 3-year disease-free survival rate | 3-year disease-free survival rate | 3 years | 
| 3-year overall survival rate | 3-year overall survival rate | 3 years | 
| 3-year recurrence pattern | 3-year recurrence pattern | 3 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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laparoscopy, minimally invasive surgical procedures, stomach neoplasm, Gastrectomy, Reflux Esophagitis