Background and purpose: Lysine specific demethylase 1(LSD1) is an important chromatin modifier. It epigenetically regulates gene expression pattern through chromatin modification and participates in maintenance of tumor malignant properties, such as oncogenesis, development, invasion, migration and metabolic transformation. SIRT3 (sirtuin 3) is a mitochondria localized tumor suppressor and regulates tumor metabolic transformation and oxidative stress. The correlation between LSD1 and SIRT3 has never been reported before. This study aimed to elucidate the correlation between LSD1 and SIRT3 with gene transcriptional regulation methods. Methods: RNA interference technique, co-immunoprecipitation assay(CoIP), chromatin immune-precipitation assay(ChIP) and ifrelfy luciferase activity assay were employed to elucidate the correlation between LSD1 and SIRT3 in pancreatic cancer. Results:mRNA and protein levels of SIRT3 were signiifcantly elevated in LSD1 knock-down PANC-1 cells. LSD1 interacts with PGC-1α, an important regulator of SIRT3 gene expression. LSD1 and PGC-1αoccupied the same region in SIRT3 promoter region through ChIP analysis. Luciferase activity assay validated LSD1 as a negative regulator of PGC-1αin SIRT3 gene transcriptional regulation. Conclusion:LSD1, as an important tumor promoter, negatively regulates the expression of tumor suppressor gene SIRT3, these results provide important clues for the role that LSD1 plays in aberrant metabolism and oxidative stress.

Background and purpose:Lower expression of E-cadherin is associated with metastasis of cancer cells, however, the correlation between E-cadherin and glucose metabolism has seldom been reported. This article studied the correlation between E-cadherin and glycolysis effect in PANC-1 cells.Methods:Through treatment of transforming growth factor β (TGF-β) in PANC-1 cells to decrease E-cadherin expression, knock-down the gene of E-cadherin interaction protein β-catenin, and overexpressing of E-cadherin, the effects of E-cadherin on the glucose uptake and lactate production ability and on the expression of key glycolytic genes were assessed.Results:E-cadherin negatively regulated the glycolytic effect of PANC-1 cells by inhibiting glucose uptake and lactate production (P<0.05). Moreover, E-cadherin interacting partner β-catenin signiifcantly promoted glucose metabolism transformation in PANC-1 cells (P<0.05). Moreover, key glycolysis regulator sirtuin 3 (SIRT3) could lower E-cadherin expression.Conclusion:Lower expression of E-cadherin induced the transformation of glucose metabolism transformation in PANC-1 cells and manipulation of E-cadherin expression level could change the glycolysis effect. Moreover, through maneuver glycolysis process could inhibit high metastatic potential of pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.

Objective To investigate the predictive value of the plasma D-dimer levels on stage and response to chemotherapy of the pancreatic cancer (PC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 212 PC patients who were admitted to the Fudan University Shanghai Cancer Center between December 2016 and May 2017 were collected.Plasma D-dimer levels of 212 patients were measured,and relationship between plasma D-dimer levels and clinicopathological features or response to chemotherapy were analyzed.Observation indicators:(1) relationship between clinicopathological features and positive rate of plasma D-dimer before treatment;(2) relationship between response to chemotherapy and plasma D-dimer levels;(3) follow-up and survival situations.Follow-up using telephone interview was performed to detect survival of patients up to January 2018.Comparisons of count data were analyzed using chi-square test.Measurement data with skewed distribution were described as M (range).Results (1) Relationship between clinicopathological features and positive rate of plasma D-dimer before treatment:positive rate of plasma D-dimer before treatment was respectively 18.37％ (9/49),43.64％ (24/55),53.85％ (28/52),80.36％ (45/56) in patients with stage Ⅰ-Ⅱ A,ⅡB,Ⅲ and Ⅳ of TNM staging and 43.59％(17/39),24.62％(16/65) in patients with low-differentiated tumor and high-and moderate-differentiated tumor,with statistically significantly differences (x2 =41.454,4.051,P＜0.05).(2) Relationship between response to chemotherapy and plasma D-dimer levels:of 212 PC patients,108 received pathological diagnosis by endoscopic ultrasonography or liver puncture,and then underwent 4-6 cycles chemotherapy with gemcitabine.Of 108 patients,response to chemotherapy of 59 patients was partial remission or stable disease,plasma D-dimer level before treatment was increased in 39 patients (28 with reduced plasma D-dimer level after treatment) and normal in 20 patients;response to chemotherapy of 49 patients was progressive disease,plasma D-dimer level before treatment was increased in 34 patients (8 with reduced plasma D-dimer level after treatment) and normal in 15 patients.There was no statistically significant difference in proportion of patients with increased plasma D-dimer level before treatment (x2=0.132,P＞0.05),and there was a statistically significant difference in proportion of patients with reduced plasma D-dimer level after treatment (x2 =16.929,P＜0.05).(3) Follow-up and survival situations:212 patients were followed up for 3.5-12.0 months,with a median time of 7.5 months.During the follow-up,7 patients died and 205 had survival.Conclusion The plasma D-dimer level is significantly associated with TNM staging of the PC,tumor differentiation and response to chemotherapy.

Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.