The aim of our study is to compare the safety and prognosis with robotic radical anterograde modular pancreaticosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SRPS) in the treatment of pancreatic body and tail cancer.
A single-center, randomized, phase III study. The study protocol adheres to the SPIRIT statement (Additional file 1).
The primary efficacy endpoint of the trial will be the rates of margins and the number of lymph node retrieval. The second endpoints are: (1) postoperative complications including pancreatic fistula, intra-abdominal abscess, and anastomotic leakage, according to the Clavien-Dindo classification（Table.1）. Complications higher than grade II are regarded as clinically significant ; (2) perioperative indicators; such as operation time, blood loss, blood transfusion volume, transition rate to open surgery, postoperative hospitalization days, hospital costs.
Determination of the postoperative marginal resection rate is the main endpoint of this study. Published literatures with large sample size (n > 100) of distal adenocarcinoma demonstrate R0 resection rate of 50%–74%[13, 14]. A systematic review of radical antegrade modular pancreatosplenectomy which identified 13 observational studies involving 354 patients undergoing RAMPS showed that the R0 resection rate was 88%  . According to these studies, we used a two-sided log-rank test with 80% power at the 0.05 level of significance requires 123 patients in each group (NCSS and PASS 11 (NCSS Statistical Software, Kaysville, UT, USA)). Therefore, the total sample size required is n = 246 patients.
- The tumor was diagnosed as resectable by preoperative pathological examination or clinical judgment
- It meets the indications of resection of pancreatic somatococcygeal carcinoma by robot;
- Postoperative pathological diagnosis of pancreatic ductal adenocarcinoma;
- Complete clinical data.
- Preoperative imaging examination or intraoperative exploration revealed distant metastasis and abandonment of surgery;
- Preoperative chemotherapy or radiotherapy;
- Patients with major complications who cannot tolerate surgery;
- Complicated with or secondary other malignant tumors.
Differences in the surgical experience of surgeons may lead to differences in the incidence of complications. To prevent surgeon bias, our doctors have experience of more than 40 RDPs. Our surgical team consists of three doctors who are all skilled at using Da Vinci robotic systems for RAMPS and SRPS. In this research, each of these clinicians meet the participation requirements and received adequate training prior to participating in the study. Patients will be randomly assigned to each doctor's surgery group.
After confirmation of the eligibility criteria, including written informed consent, registration is made to the central registry in Chinese PLA General Hospital (CPGH). Each patient will be randomly assigned a number in the central registry. Then patients are randomized in a 1:1 allocation ratio to either arm A (RAMPS) or arm B (SRPS) with a random block size. (Fig.1)
Data collection and statistics
All patients will be prospectively collected, including history, physical examination, laboratory data, pathological examination, perioperative clinical information, and complications. Data will be collected and stored securely through computer data sheets. All enrolled cases will be managed by randomly assigned CPGH codes. The corresponding tables of codes and informed consent forms will be kept strictly in the CPGH file library. All required parameters will be collected in SPSS data files (SPSS version 25, IBM statistics, Chicago, IL, USA).
An independent research physician (SBP) will not be involved in the treatment and monitoring of patients in the surgical room and enter all necessary data into the prepared CRF. The CRF will be completed as soon as possible, preferably on the day of patient treatment and visit (Table. 2). Reasonable explanations should be given for all missing data. The complete CRF page will be examined for completeness and reasonableness by the principal investigator and responsible supervisors.
Robotic radical antegrade modular pancreatosplenectomy
All RDP procedures will be performed using the da Vinci™ Si Surgical System (Intuitive, Sunnyvale, CA, USA). After the general anesthesia is effective, the patient is placed in a supine position. Our surgical procedures of RDPS and LDPS have been described previously[16, 17]. The layout of Trocar is shown in Fig.2. Diagnostic laparoscopy is performed to rule out metastasis. Open gastric colon ligament and separate the superior mesenteric vein at the lower margin of the pancreatic neck. The little omentum capsule is then opened to dissect the common hepatic artery, and para-hepatic arterial lymph nodes are dissected (groups 8a and 8p). The gastroduodenal artery is isolated, and then the superior portal vein of the pancreas is exposed. Establish the pancreatic neck tunnel and disconnect the pancreatic neck. Lymph nodes around the celiac trunk (9 groups) and fibrous adipose tissue are dissected. The splenic artery is isolated along the celiac trunk, ligate and sever in the root, and the left gastric artery is severed when necessary. The distal pancreas is pulled from right to left, the splenic vein is severed from the root, and the proximal end is closed with 5-0prolene continuous suture. Lymph nodes are dissected downward from the celiac trunk and the periceliac nerve plexus to the superior mesenteric artery, and the left lymph node of the superior mesenteric artery is dissected (group 14c and group 14d). Continue dissecting posteriorly and reveal the leading edge of the left renal vein and left adrenal vein. The specimen is redirected to the left to ensure that the anatomical resection plane is located behind Gerota's fascia. The anterior approach should be close to the left renal vein, renal capsule and the front edge of the left adrenal surface to clear the retroperitoneal tissue (this is the anterior RAMPS). The posterior approach requires resection of the left adrenal gland and its surrounding tissue (posterior RAMPS). At the same time, the upper and lower edges of the pancreas are freed, and then the ligaments around the spleen are removed, and the specimen is finally removed.
Robotic standard retrograde pancreatosplenectomy
Anesthesia and trocar are arranged as RAMPS described above. Open the colon ligaments and then separate the spleen-stomach ligaments, the splenic-colonic ligaments, and the splenic-diaphragmatic ligaments to free the spleen. The pancreas is separated from the retroperitoneum from the left to the right and disconnect the pancreas about 2 cm away from the distal end of the tumor. Then suture pancreatic stump to stop bleeding.
A drainage tube will be placed to assess the PF as the primary endpoint before the abdomen is closed. The number and location of the inserted drainage tubes will be recorded in the data sheet. And we will specify when to remove the drain.
Concurrent and supportive treatments
Antibiotics, blood products, analgesics, H2 blockers and proton pump inhibitors will be determined by the surgeon for intraoperative and postoperative management. In addition, there are no regulations for drugs used to control complications and adverse events. Records are given for specific adverse events.