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PURPOSE: Although laparoscopic pancreaticoduodenectomy (LPD) is increasingly performed in high-volume centers, pancreaticojejunostomy (PJ) is still the most challenging procedure. Pancreatic anastomotic leakage remains a major complication after PD. Thus, various technical modifications regarding PJ, such as the Blumgart technique, have been attempted to simplify the procedure and minimize anastomotic leakage. Three-dimensional (3D) laparoscopic systems have been shown to be particularly helpful in performing difficult and precise tasks. We present a modified Blumgart anastomosis in 3D-LPD and investigate its clinical outcomes. METHODS: A retrospective analysis of 100 patients who underwent 3D-LPD with modified Blumgart PJ from September 2018 to January 2020 was conducted. Data on the preoperative characteristics, operative outcomes, and postoperative characteristics of the patients were collected and analyzed. RESULTS: The mean operative time and duration of PJ were 348.2 and 25.1 min, respectively. The mean estimated blood loss was 112 mL. The overall rate of postoperative complications over Clavien‒Dindo classification III was 18%. The incidence of clinically relevant postoperative pancreatic fistula was 11%. The median postoperative hospital stay was 14.2 days. Only one patient required reoperation (1%), and no patient died in the hospital or 90 days after the operation. High BMI, small main pancreatic duct diameter, and soft pancreatic consistency had a significant influence on the occurrence of CR-POPF. CONCLUSIONS: The surgical outcome of 3D-LPD with modified Blumgart PJ seems to be comparable to other studies in terms of operation time, blood loss, hospital stay, and complication incidence. We consider the modified Blumgart technique in 3D-LPD to be novel, reliable, safe, and favorable for PJ in the PD procedure.

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Laparoscopía , Pancreatoyeyunostomía , Humanos , Pancreatoyeyunostomía/efectos adversos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Fuga Anastomótica/etiología , Estudios Retrospectivos , Anastomosis Quirúrgica/métodos , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/etiología , Laparoscopía/efectos adversos , Laparoscopía/métodos

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BACKGROUND: Methyl-CpG binding domain protein 1 (MBD1), which couples DNA methylation to transcriptional repression, has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell cycle progression and development. It has also been proven that MBD1 is involved in tumor development and progression. However, whether MBD1 is involved in tumorigenesis, especially in gallbladder cancer, is totally unknown. METHODS: Human GBC-SD and SGC996 cells were used to perform experiments. Invasion, wound healing and colony formation assays were performed to evaluate cell viability. A CCK-8 assay was performed to assess gallbladder cancer cell viability after gemcitabine treatment. Western blot analysis was used to evaluate changes in protein expression. Human gallbladder cancer tissues and adjacent nontumor tissues were subjected to immunohistochemical staining to detect protein expression. RESULTS: We found that MBD1 expression was significantly upregulated in gallbladder cancer tissues compared with that in surrounding normal tissues according to immunohistochemical analysis of 84 surgically resected gallbladder cancer specimens. These data also indicated that higher MBD1 expression was correlated with lymph node metastasis and poor survival in gallbladder cancer patients. Overexpression and deletion in vitro validated MBD1 as a potent oncogene promoting malignant behaviors in gallbladder cancer cells, including invasion, proliferation and migration, as well as epithelial-mesenchymal transition. Studies have demonstrated that epithelial-mesenchymal transition is common in gallbladder cancer, and it is well known that drug resistance and epithelial-mesenchymal transition are very closely correlated. Herein, our data show that targeting MBD1 restored gallbladder cancer cell sensitivity to gemcitabine chemotherapy. CONCLUSIONS: Taken together, the results of our study revealed a novel function of MBD1 in gallbladder cancer tumor development and progression through participation in the gallbladder cancer epithelial-mesenchymal transition program, which is involved in resistance to gemcitabine chemotherapy. Thus, MBD1 may be a potential therapeutic target for gallbladder cancer.

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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.

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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.

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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.

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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.