Study on Laparoscopic Spleen-Preserving No. 10 Lymph Node Dissection for Advanced Gastric Cancer (CLASS-04)

Safety and Feasibility of Laparoscopic Spleen-Preserving No. 10 Lymph Node Dissection for Locally Advanced Upper Third Gastric Cancer: A Multicenter Phase II Trial

Peking University Cancer Hospital & Institute, Southwest Hospital, China, Fujian Provincial Hospital, Zhangzhou Municipal Hospital of Fujian Province, Shanghai Zhongshan Hospital, Meizhou People's Hospital, Guangdong Provincial People's Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine, Second Hospital of Jilin University, The First Affiliated Hospital with Nanjing Medical University, Nanfang Hospital, Southern Medical University, Affiliated Hospital of Qinghai University, The First Affiliated Hospital of Xiamen University, RenJi Hospital, West China Hospital, First Affiliated Hospital Xi'an Jiaotong University, First Affiliated Hospital of Xinjiang Medical University, The First Hospital of Putian City, Putian, Fujian, Longyan City First Hospital

The purpose of this study is to explore the safety and feasibility of the Laparoscopic Spleen-Preserving No. 10 Lymph Node Dissection for patients with locally advanced upper third gastric adenocarcinoma（cT2-4a, N-/+, M0）.

Radical resection is still the primary method of treating advanced gastric cancer.According to the Japanese treatment guidelines for gastric cancer, D2 lymphadenectomy, including No. 10 lymph node dissection, should be adopted for upper third gastric carcinoma.The incidence of No. 10 lymph node metastasis is high in advanced proximal gastric cancer, reported to range from 9.8%-20.9%, and the presence of No. 10 lymph node metastasis is closely related to survival. Therefore, in East Asia, D2 lymph node dissection of potentially curable locally advanced upper third gastric cancer including No. 10 lymph node is the standard surgical treatment. In the early, splenectomy was performed to remove No. 10 lymph node. With the improvement of medical knowledge and surgical technique, spleen-preserving No. 10 lymph node dissection has been recognized by more and more surgeons. However, due to the special and complex anatomy of the spleen, spleen-preserving No. 10 lymph node dissection is difficult, even in open surgery; consequently, the surgery cannot be performed in many centers. Laparoscopic surgery has distinct minimally invasive advantages, such as small incisions, less blood loss, less postoperative pain, mild postoperative inflammatory reactions, a quick recovery of gastrointestinal function, shorter hospital stays and obvious cosmetic effects. Since Kitano et al. first reported laparoscopic gastrectomy for gastric cancer in 1994, laparoscopic techniques have developed rapidly. The techniques are becoming increasingly mature, making it possible to perform laparoscopic spleen-preserving No. 10 lymph node dissection. Our center first proposed "Huang's three-step maneuver", a new operative method suitable for laparoscopic spleen-preserving No. 10 lymph node dissection. This method simplifies the procedure of laparoscopic spleen-preserving No. 10 lymph node dissection and facilitates its popularization and promotion. However, it remains a controversial international issue if it is safe and feasible to routinely conduct laparoscopic spleen-preserving No. 10 lymph node dissection for advanced upper third gastric cancer.A number of retrospective studies have successively confirmed the safety, feasibility and oncological efficacy of laparoscopic spleen-preserving No. 10 lymph node dissection.But there is no multicenter prospective studies to identify the results. Therefore, The study is through a prospective, multicenter, open, single-arm, non-inferiority study,to explore the safety and feasibility of the laparoscopic spleen-preserving No. 10 lymph node dissection for patients with locally advanced upper third gastric adenocarcinoma（cT2-4a, N-/+, M0）.

Patients with locally advanced upper third gastric carcinoma will performed laparoscopic spleen-preserving No.10 lymph node dissections.After the surgery the patients will be treated with oxaliplatin or platinum-based chemotherapy.

After exclusion of T4b, bulky lymph nodes, or distant metastasis case et al. Laparoscopic spleen-preserving No.10 lymph node dissections will be performed with curative treated intent in patients with locally advanced upper third gastric adenocarcinoma.

oxaliplatin or platinum-based chemotherapy is used when the patients undergo adjuvant chemotherapy after the surgery.

Refers to the incidence of early postoperative complications. The early postoperative complication are defined as the event observed within 30 days after surgery.

The Rates of positive No.10 lymph node are defined as the incidence of positive No.10 lymph node (divide number of positive No.10 lymph nodes by number of total No.10 lymph nodes).

Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type.

The intraoperative postoperative morbidity rates are defined as the rates of event observed within operation.

Visual analog pain score method is used to evaluate the difference of postoperative pain degree.The score of postoperative pain is used to assess the postoperative recovery course.

The variation of weight on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.

The variation of cholesterol in millimole/liter on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.

The variation of album in gram/liter on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.

The incidence of reflux esophagitis under the endoscopy on postoperative 3 and 12 months are used to access the postoperative quality of life.

The daily highest body temperature in degree centigrade before discharge are recorded to access the inflammatory and immune response.

The values of white blood cell count from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.

The values of hemoglobin in gram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.

The values of C-reactive protein IN milligram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.

The values of prealbumin in gram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.

Inclusion Criteria: Age between 18 to 75 years old Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by endoscopic biopsy Locally advanced tumor in the upper third stomach（cT2-4a, N-/+, M0 at preoperative evaluation according to the AJCC(American Joint Committee on Cancer) Cancer Staging Manual Seventh Edition） No distant metastasis, no direct invasion of pancreas, spleen or other organs nearby in the preoperative examinations Performance status of 0 or 1 on ECOG (Eastern Cooperative Oncology Group) scale ASA (American Society of Anesthesiology) class I to III Written informed consent Exclusion Criteria: Pregnant and lactating women Suffering from severe mental disorder History of previous upper abdominal surgery (except for laparoscopic cholecystectomy) History of previous gastric surgery (including ESD/EMR (Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection )for gastric cancer) Enlarged or bulky regional lymph node （diameter over 3cm）supported by preoperative imaging including enlarged or bulky No.10 lymph node History of other malignant disease within the past 5 years History of previous neoadjuvant chemotherapy or radiotherapy History of unstable angina or myocardial infarction within the past 6 months History of cerebrovascular accident within the past 6 months History of continuous systematic administration of corticosteroids within 1 month Requirement of simultaneous surgery for other disease Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer FEV1<50% of the predicted values Splenectomy must be performed due to the obvious tumor invasion in spleen or spleen blood vessels.

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