Pancreatic cancer is currently recognized as one of the most malignant solid tumors， with a 5-year survival rate of 13% over a long period of time， and 80% of the patients have lost the opportunity for surgery at the time of confirmed diagnosis. In addition， the efficacy of conventional radiochemotherapy and targeted therapy is limited by high tumor heterogeneity and the complex immunosuppressive microenvironment. In recent years， mRNA vaccines have become a new focus of tumor immunotherapy due to their unique technical advantages. Based on non-integrating mRNA templates， mRNA vaccines enable precise encoding of tumor neoantigens， which are efficiently expressed in the host and can induce multifaceted immune responses. As for pancreatic cancer， current studies mainly focus on the development and optimization of tumor-associated antigen vaccines and tumor-specific antigen vaccines， as well as next-generation sequencing-guided neoantigen epitope optimization， innovative targeted delivery systems， and artificial intelligence-powered predictive models for immune response， thereby promoting the application of mRNA vaccines in the precise treatment of pancreatic cancer. Further studies should make breakthroughs in the targeted blockade of critical immunosuppressive molecules within the tumor microenvironment， the precise identification of tumor-specific antigenic epitopes， and the development of highly efficient vaccines， so as to bring new hopes for patients with pancreatic cancer.

Objective:To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP).Methods:This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the 1 211 patients,440 cases were in the robot-assisted group(173 males and 267 females),with an age( M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ 2 test,while multivariate analysis utilized binary logistic regression. Results:After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor: χ 2=1.200, P=0.952;malignant tumor: χ 2=0.391, P=0.532). The surgical duration of the RDP group ( Z 1=15.113, P 1<0.01; Z 2=4.232, P 2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss ( Z 1=12.530, P 1<0.01; Z 2=2.550, P 2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group ( Z 1=10.947, P 1<0.01), but not different from that in the laparoscopic group ( P 2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender( χ 2=12.048, P=0.001),history of smoking ( χ 2=6.327, P=0.012),history of alcohol consumption ( χ 2=17.597, P<0.01),manual pancreas division ( χ 2=9.839, P=0.002),early elevation of amylase in drainage fluid ( Z=5.187, P<0.01),and delayed gastric emptying ( χ 2=4.485, P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption( P=0.002,95% CI: 0.112 to 0.623), manual pancreas division( P=0.001,95% CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml( P<0.01,95% CI:0.151 to 0.438),and delayed gastric emptying ( P=0.020, 95% CI: 1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusion:Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

Due to the characteristics of the insidious onset,difficult early diagnosis and high malignancy of pancrea-tic cancer,only a minority of patients still have the chance of surgical resection at the time of diagnosis.In recent years,chemotherapy-based preoperative neoadjuvant therapy has been increasingly applied to pancreatic cancer without distant metastases to help achieve tumor downstaging,increase RO resection rate and improve patient survival.A large number of clinical trials have proven the advantages of neoadjuvant therapy for pancreatic cancer,but there are still many issues to be gradually addressed by further research to reach a consensus.

Objective:To explore the safety and efficacy of Tumai domestic multi-port robot-assisted surgery system in the clinical application of distal pancreatectomy in pancreatic tumor patients.Methods:A prospective, single-center, single-arm exploratory study was conducted. A total of 20 patients who underwent robot-assisted pancreatic body-tail resection in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2023 to November 2023 were enrolled, including 13 males and 7 females, aged (57.9±11.2) years. All the patients underwent robot-assisted distal pancreatectomy with Tumai multi-port surgical robot. Clinical data of complications, intraoperative blood loss, operative time, postoperative drainage tube retention time, and postoperative pathology were collected and statistically analyzed.Results:All the 20 patients underwent surgery successfully. Only 1 patient (5.0%) was diagnosed with pancreatic neuroendocrine tumor (G1 stage), and the rest were benign pancreatic tumors, including serous cystadenoma and mucinous cystadenoma. No instrument-related organ or blood vessel injury occurred, no intraoperative complications occurred. Of 7 patients (35.0%) had postoperative complications, including 3 infections, 3 abdominal effusion, and 1 hypokalemia. According to the Clavien-Dindo grading, all the cases were grade Ⅰ except 1 case with grade Ⅱ abdominal effusion. No serious complications above grade Ⅲ occurred. The intraoperative blood loss of the 20 patients was 100(20, 200) ml, the operative time was (125.7±76.9) min, and the postoperative retention time of drainage tube was (7.9±3.4) d.Conclusion:Tumai domestic multi-port robot-assisted surgery system has acceptable safety and efficacy in the clinical application of distal pancreatectomy.

Objective:To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP).Methods:This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the 1 211 patients,440 cases were in the robot-assisted group(173 males and 267 females),with an age( M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ 2 test,while multivariate analysis utilized binary logistic regression. Results:After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor: χ 2=1.200, P=0.952;malignant tumor: χ 2=0.391, P=0.532). The surgical duration of the RDP group ( Z 1=15.113, P 1<0.01; Z 2=4.232, P 2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss ( Z 1=12.530, P 1<0.01; Z 2=2.550, P 2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group ( Z 1=10.947, P 1<0.01), but not different from that in the laparoscopic group ( P 2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender( χ 2=12.048, P=0.001),history of smoking ( χ 2=6.327, P=0.012),history of alcohol consumption ( χ 2=17.597, P<0.01),manual pancreas division ( χ 2=9.839, P=0.002),early elevation of amylase in drainage fluid ( Z=5.187, P<0.01),and delayed gastric emptying ( χ 2=4.485, P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption( P=0.002,95% CI: 0.112 to 0.623), manual pancreas division( P=0.001,95% CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml( P<0.01,95% CI:0.151 to 0.438),and delayed gastric emptying ( P=0.020, 95% CI: 1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusion:Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

Objective:To investigate the prognosis of robotic pancreatoduodenectomy after the learning curve and open pancreatoduodenectomy for pancreatic cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 396 patients who underwent curative pancreatoduodenectomy for pancreatic duct adenocar-cinoma in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from January 2017 to December 2018 were collected. There were 244 males and 152 females, aged 64(range, 36?92)years. Of 396 patients, 86 cases undergoing robotic pancreatoduodenectomy were divided into robotic group, 310 cases undergoing open pancreatoduodenectomy were divided into open group. Observa-tion indicators: (1) propensity score matching and comparison of general data between the two groups after matching; (2) follow-up and survival analysis. Follow-up was conducted by telephone interview or outpatient examinations including tumor markers and abdominal imaging examina-tions to detect survival of patients up to March 2022. Overall survival was defined as the time from the surgery date to death or the last follow-up. Disease-free survival was defined as the time from the surgery date to tumor recurrence or the last follow-up. The propensity score matching was conducted by 1∶1 matching using the nearest neighbor method. Normality of measurement data was examined using the Shapiro-Wilk test. Measurement data with skewed distribution were described as M(range), and comparison between groups was analyzed using the Mann-Whitney rank-sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used for survival analysis. An intent-to-treat analysis was performed in this study, patients who were converted to laparotomy from robotic surgery were still divided into the robotic group. Results:(1) Propensity score matching and comparison of general data between the two groups after matching: 164 of 396 patients had successful matching, including 82 cases in robotic group and open group, respectively. Before propensity score matching, the body mass index, cases in stage T1, T2, T3, T4, cases in N0, N1, N2 were 23.4(range, 21.4?25.3)kg/m 2,24, 41, 10, 11, 52, 27, 7 for the robotic group, versus 22.4(range,20.3?23.9)kg/m 2,57, 144, 22, 87, 131, 132, 47 for the open group, showing significant differences in the above indicators between the two groups ( Z=3.01, 2.63, 3.03, P<0.05). After propensity score matching, cases of males, age, body mass index, cases with American Society of Anesthesiologists (ASA) score as 1, 2, 3, CA19-9, cases with preoperative biliary drainage, cases with portal vein resection, cases with pancreatic resection margin <1 mm, cases in stage T1, T2, T3, T4, cases in stage N0, N1, N2, cases with nerve invasion, cases with tumor differentiation as high-medium differentiation, medium-low differentiation, low differentiation, cases with adjuvant chemotherapy were 51, 65(range, 59?69)years, 23.0(range, 21.0?25.2)kg/m 2, 32, 41, 9, 160.4(range, 46.7?377.2)U/mL, 21, 9, 8, 21, 40, 10, 11, 48, 27, 7, 76, 26, 47, 9, 53 for the robotic group, versus 58, 65(range, 58?69)years, 23.3(range, 21.4?25.3)kg/m 2, 35, 39, 8, 172.0(range, 69.7?402.9)U/mL, 26, 9, 10, 24, 40, 7, 11, 49, 28, 5, 76, 22, 49, 11, 57 for the open group, showing no significant difference in the above indicators between the two groups ( χ2=1.34, Z=0.18, 0.34, 0.49, 0.51, χ2=0.75, 0.00,0.25, Z=0.59, 0.27, χ2=0.00, Z=0.76, χ2=0.44, P>0.05). (2) Follow-up and survival analysis: after propensity score matching, 164 patients were followed up for 54(range, 1?67)months. The follow-up time of patients was 55(range, 51?59)months for the robotic group, versus 54(range, 50?58)months for the open group, respectively, showing no significant difference between the two groups ( Z=0.48, P>0.05). During the follow-up, the 1-year overall survival rate, 3-year overall survival rate, the median survival time, 1-year disease-free survival rate, 3-year disease-free survival rate, the median disease-free survival time, tumor recurrence rate, cases with recurrence pattern as local recurrence, liver recurrence, other distant recurrence, local and distant recurrence were 81.7%, 39.0%, 27 months(95% confidence interval as 19?33 months), 61.0%, 34.2%, 15 months(95% confidence interval as 12?18 months), 54.9%(45/82), 12, 16, 9, 8 for the robotic group. The above indicators were 79.3%, 36.0%, 24 months(95% confidence interval as 19?31 months), 59.8%, 27.5%, 15 months(95% confidence interval as 10?20 months), 58.5% (48/82), 10, 22, 6, 10 for the open group. There was no significant difference in overall survival or disease-free survival between the two groups ( χ2=0.39, 0.47, P>0.05). There was no significant difference in tumor recurrence rate or tumor recurrence site between the two groups either ( χ2=0.22, 1.86, P>0.05). Conclusion:After the learning curve, robotic pancreato-duodenectomy has non-inferior prognosis compared with open pancreatoduodenectomy.

Objective To establish the diagnostic model based on detection of serum biomarkers in pancreatic cancer (PC) associated diabetes.Methods From June 2013 to July 2014, at Ruijin Hospital, School of Medicine , Shanghai Jiao Tong University , 30 patients diagnosed with PC companied with new onset diabetic mellitus and 30 patients with new onset type 2 diabetic mellitus , were enrolled .Serum samples were examined by liquid chromatography-mass spectrometry ( LC-MS) for metabolomics analysis .Orthogonal partial least square ( OPLS ) was performed for raw data analysis to obtain the differentially expressed metabolites between two groups .The first 15 cases of each group were taken as training samples and the left as validation samples.The model was established using logistic regression via stepwise differentially expressed metabolites and clinical data input in training samples .The diagnostic efficiency of the model was verified in validating samples . Results Ten differentially expressed metabolites were identified in PC companied with new onset diabetic mellitus group and new onset type 2 diabetic mellitus group .The differentially expressed metabolites identified in positive ion mode were 3-ketosphingosine , arachidonoyl dopamine , phosphatidylethanolamine ( 18 :2 ) , ubiquinone-1 and valine .The differentially expressed metabolites identified in negative ion mode were C 16 sphingosine-1-phosphate, keto palmitic acid, isoleucine, N-succinyl-L-diaminopimelic acid and uridine.The diagnostic model was established in training samples:p=e(Xβ)/(1+e(Xβ)), ( Xβ) =-158.975-1.891 (age) +0.309 ( phosphatidylethanolamine 18:2 ) +1.035 ( C16 sphingosine-1-phosphate ) +0.084 (isoleucine) +1.1145 ( N-succinyl-L-diaminopimelic acid ).The area under curve ( AUC) of receiver operating characteristic (ROC) of this model was 0.982 in validation samples, the sensitivity and specificity were both 93.3％.Conclusion Serum metabolomics-based diagnostic approach is a promising method for screening PC from new onset diabetic mellitus .

Pancreaticoduodenectomy (PD) is a standard surgical method for periampullary cancer.The hemorrhage is a dangerous complication after PD,how to effectively prevent and treat hemorrhage is a difficult point of pancreatic surgery,and also a key for reducing postoperative mortality.Four famous experts and their teams in surgical fiell explored prevention and treatment of the hemorrhage after PD from different angles based on clinical experiences.Professor Shen Boyong has conducted a discussion on early and Date hemorrhage after PD combined with previous successful experiences and prospective research data.Professor Chen Yajin suggested preventing hemorrhage in the aspects of anatomical resection,anastomosis and reconstruction,peritoneal drainage-tube placement and postoperative management based on different causes of hemorrhage.Professor Peng Bing paid attention to hemorrhage after laparoscopic PD,and supposed that intraoperative careful hemostasis,precise anastomosis,reasonable peritoneal drainage-tube placement and optimal perioperative management can reduce incidences of postoperative pancreatic fistula,biliary fistula and intra-abdominal infection,thereby lowering the incidence of hemorrhage.Professor Tan Guang respectively proposed processing strategies of hemorrhagc for grading A (mild at early stage),B (severe at early stage and mild at late stage) and C (severe at late stage).

Chylous fistula is a postoperative complication following pancreatic surgery,it is mainly diagnosed according to the nature of the patient's drainage fluid (≥3 days after surgery,triglyceride concentration ≥ 1.2 mmol/L).The mechanism of occurrence includes obstruction,injury and exudation of the lymph-vessels.Risk factors can be concluded into 3 aspects:clinicopathological features,surgical procedure and postoperative management.Most of the chylorrhea can be cured by conservative treatment like modified dietary measures and somatostatin,while severe cases still requires intervention and surgical treatment.This article reviewed the risk factors and treatment approaches of postoperative chylous fistula,and elucidated relative mechanisms,hoping to provide guidance in clinical prevention,diagnosis and treatment of chylous fistula.

With the continuous improvement of the diagnosis rate of benign pancreatic disease and the younger age of disease onset,the demand for minimally invasive pancreatic surgery is increasing,meanwhile,how to keep the normal pancreatic tissue as much as possible to reduce the impact on the patients' life has gained surgeons' thinking.The Da Vinci robotic surgical system,providing a clearer 3D vision and more accurate operation,makes some difficult minimally invasive pancreatic surgery such as pancreaticoduodenectomy can be carried out extensively.Based on clinical experiences and related literatures,this paper will analyze the present situation of Da Vinci robot-assisted pancreatic surgery and give prospects.