- Email: [email protected]
Systematic review and meta-analysis of pancreatic amylase value on postoperative day 1 after pancreatic resection to predict postoperative pancreatic fistula
Abstracts / Pancreatology 16 (2016) S1eS63
in an accurate and timely manner because of the long follow-ups and bias from multiple second-line chemotherapies. Therefore, we performed a meta-analysis based on Phase III randomized clinical trials of first-line treatment in LAMPC to examine whether progression-free survival (PFS), response rate (RR), or time to progression (TTP) were appropriate surrogate endpoints (SEP) for overall survival (OS). Methods: All Phase III randomized clinical trials of first-line treatments in advanced and metastatic pancreatic cancer were evaluated. Characteristics and outcomes of RR, TTP, PFS and OS were extracted and calculated. Summary data were analyzed using linear regression. The rank correlation coefficients (Prs, Pearson rank correlation coefficient, and Srs, nonparametric Spearman), and WLS R2 (weighted linear regression) were used to assess surrogacy. Results: Twenty-eight randomized trials containing 11,726 LAMPCs were analyzed. The logarithm of the hazard ratio for PFS (LogPFSHR) was highly correlated with the logarithm of the hazard ratio for OS (LogOSHR) (Prs¼0.915, p<0.001; WLS R2¼0.841). DPFS exhibited a good correlation with DOS (Srs¼0.784, p<0.001; WLS R2¼0.643). The odds ratio (OR) of the disease control ratio (DCR) was also correlated with the HR of OS (Prs¼0.795, p¼0.001, WLS R2¼0.538). Conclusions: PFS is a reliable SEP for OS when assessing the first-line treatment effect of chemotherapy in patients with LAMPC regardless of response criteria and chemotherapy regimens.
S23
Functionally, upregulation of miR-329 inhibited proliferation and induced apoptosis of pancreatic cancer cells in vitro, and that was further validated in the primary pancreatic cancer cells. In vivo, reexpression of miR-329 significantly inhibited the tumor formation in xenograft mice. We identified GRB2 as a target of miR-329 with luciferase activity assay and western blot. Importantly, the expression of GRB2 can partially rescue the antiproliferation function of miR-329. And in pancreatic cancer tissues, GRB2 expression inversely correlated with miR-329 levels. Conclusions: Our findings suggest that miR-329 attenuates the proliferation and induces apoptosis of pancreatic cancer cells by targeting GRB2. Keywords: Pancreatic cancer, miR-329, GRB2, Growth, Apoptosis
15287. Systematic review and meta-analysis of pancreatic amylase value on postoperative day 1 after pancreatic resection to predict postoperative pancreatic fistula Xiongxiong Lu 1, Xinjing Wang 1, Hao Chen, Chenghong Peng, Hongwei Li, Yuan Fang, Xiaxing Deng*, Baiyong Shen* E-mail address: [email protected], [email protected]
15286. MiR-329 restricts tumor growth by targeting GRB2 in pancreatic cancer Xinjing Wang 1, 2, 3,#, Xiongxiong Lu 1,2, 3, #, Tian Zhang 1, 2, 3, #, Chenlei Wen 1, 2, 3, Minmin Shi 3, Xiaomei Tang 1, 2, 3, Hao Chen 1, 2,3, Chenghong Peng 1, 2, 3, Hongwei Li 1, Yuan Fang 1, 2, 3,*, Xiaxing Deng 1, 2, 3, *, Baiyong Shen 1,2, 3, * 1 Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 2 Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 3 Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
E-mail address: [email protected], [email protected], shenby@ shsmu.edu.cn
Abstract Objective: Pancreatic cancer is one of the most lethal malignancies with an unacceptable poor prognosis. Recently many studies have emerged and implicated that abnormal miRNAs expression are involved in the pancreatic tumor growth and development. MiR-329 was reported as a suppressor which can inhibit various cancers including gastric cancer, neuroblastoma and glioma. However, the role of miR-329 in pancreatic cancer is still elusive. Here we intended to give a interpret about the potential function and mechanism of miR-329 in pancreatic cancer cells. Methods: qRT-PCR was performed to determine the expression level of miR-329 and its target gene in pancreatic cancer tissues and cell lines. Patients' survival was analyzed with the Kaplan-Meier method. Correlation between miR-329 and clinicopathological characteristics were determined by the Pearson c2 test. Mimic was employed to upregulate miR-329 expression. Biological function of miR-329 was examined by cell growth assay, plate clone formation assay and apoptosis analysis in vitro and xenograft tumor growth assay in vivo. Primary pancreatic cancer cells were cultured to further validate its function. Bioinformatic analysis was applied to seek the target gene of miR-329. Target gene was finally identified by luciferase activity assay and western blot. Results: MiR-329 expression was significantly downregulated in pancreatic cancer tissues when compared with paired normal tissues.
* Corresponding authors. These authors contributed equally to this work.
#
Abstract Objective: The aim of this study was to evaluate the diagnostic accuracy of drain/plasma pancreatic amylase values on postoperative day 1 (DPA1/PPA1) in POPF by means of a systemic review and meta-analysis. Methods: Online journal databases and a manual search up to April 2015 were used. Studies clearly documenting DPA1 or PPA1 in predicting overall POPF (Grade 0 vs AþBþC) or clinically relevant POPF (Grade 0þA vs BþC) following pancreatic surgery were selected. Pooled predictive parameters were performed using STATA 12.0. Results: 15 studies were finally identified with a total of 4331 patients. Pooled sensitivity and specificity of DPA1 were 0.92 (95% CI 0.81-0.96) and 0.77 (95% CI 0.64-0.86) for predicting overall POPF and 0.79 (95% CI 0.610.90) and 0.83 (95% CI 0.74-0.89) for predicting clinically relevant POPF. The pooled sensitivity and specificity of PPA1 were 0.74 (95% CI 0.63-0.82) and 0.62 (95% CI 0.55-0.70) for POPF. After the DPA1 at/over cutoff values for overall POPF or clinically relevant POPF, corresponding post-test probability (Post-test (þ)) (if pre-test probability was 50%) was 80% and 82% respectively, while, if values were below the cutoff values, the posttest probability (Post-test (-)) was 10% and 20% respectively. Pveost-test (þ) and Post-test (-) of PPA1 for overall POPF were 66% and 30% respectily. Conclusion: DPA1 is a useful predictive test for overall POPF and clinically relevant POPF which has good sensitivity and specificity based on the current studies. Meanwhile, it should be cautiously applied to clinical practice because cutoffs had a wide range between studies. Keywords: Pancreatic resection; Early drain removal; Drain amylase; Serum amylase; Pancreatic fistula
15288. Artery-first approach pancreaticoduodenectomy with extended retroperitoneal clearence (AFPD-ERC) K. Jiang, J. Wu, W. Gao, J. Chen, J. Wei, F. Guo, Z. Lu, P. Wu, Y. Miao Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
* Corresponding authors. 1 These authors contributed equally to this work.
in an accurate and timely manner because of the long follow-ups and bias from multiple second-line chemotherapies. Therefore, we performed a meta-analysis based on Phase III randomized clinical trials of first-line treatment in LAMPC to examine whether progression-free survival (PFS), response rate (RR), or time to progression (TTP) were appropriate surrogate endpoints (SEP) for overall survival (OS). Methods: All Phase III randomized clinical trials of first-line treatments in advanced and metastatic pancreatic cancer were evaluated. Characteristics and outcomes of RR, TTP, PFS and OS were extracted and calculated. Summary data were analyzed using linear regression. The rank correlation coefficients (Prs, Pearson rank correlation coefficient, and Srs, nonparametric Spearman), and WLS R2 (weighted linear regression) were used to assess surrogacy. Results: Twenty-eight randomized trials containing 11,726 LAMPCs were analyzed. The logarithm of the hazard ratio for PFS (LogPFSHR) was highly correlated with the logarithm of the hazard ratio for OS (LogOSHR) (Prs¼0.915, p<0.001; WLS R2¼0.841). DPFS exhibited a good correlation with DOS (Srs¼0.784, p<0.001; WLS R2¼0.643). The odds ratio (OR) of the disease control ratio (DCR) was also correlated with the HR of OS (Prs¼0.795, p¼0.001, WLS R2¼0.538). Conclusions: PFS is a reliable SEP for OS when assessing the first-line treatment effect of chemotherapy in patients with LAMPC regardless of response criteria and chemotherapy regimens.
S23
Functionally, upregulation of miR-329 inhibited proliferation and induced apoptosis of pancreatic cancer cells in vitro, and that was further validated in the primary pancreatic cancer cells. In vivo, reexpression of miR-329 significantly inhibited the tumor formation in xenograft mice. We identified GRB2 as a target of miR-329 with luciferase activity assay and western blot. Importantly, the expression of GRB2 can partially rescue the antiproliferation function of miR-329. And in pancreatic cancer tissues, GRB2 expression inversely correlated with miR-329 levels. Conclusions: Our findings suggest that miR-329 attenuates the proliferation and induces apoptosis of pancreatic cancer cells by targeting GRB2. Keywords: Pancreatic cancer, miR-329, GRB2, Growth, Apoptosis
15287. Systematic review and meta-analysis of pancreatic amylase value on postoperative day 1 after pancreatic resection to predict postoperative pancreatic fistula Xiongxiong Lu 1, Xinjing Wang 1, Hao Chen, Chenghong Peng, Hongwei Li, Yuan Fang, Xiaxing Deng*, Baiyong Shen* E-mail address: [email protected], [email protected]
15286. MiR-329 restricts tumor growth by targeting GRB2 in pancreatic cancer Xinjing Wang 1, 2, 3,#, Xiongxiong Lu 1,2, 3, #, Tian Zhang 1, 2, 3, #, Chenlei Wen 1, 2, 3, Minmin Shi 3, Xiaomei Tang 1, 2, 3, Hao Chen 1, 2,3, Chenghong Peng 1, 2, 3, Hongwei Li 1, Yuan Fang 1, 2, 3,*, Xiaxing Deng 1, 2, 3, *, Baiyong Shen 1,2, 3, * 1 Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 2 Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 3 Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
E-mail address: [email protected], [email protected], shenby@ shsmu.edu.cn
Abstract Objective: Pancreatic cancer is one of the most lethal malignancies with an unacceptable poor prognosis. Recently many studies have emerged and implicated that abnormal miRNAs expression are involved in the pancreatic tumor growth and development. MiR-329 was reported as a suppressor which can inhibit various cancers including gastric cancer, neuroblastoma and glioma. However, the role of miR-329 in pancreatic cancer is still elusive. Here we intended to give a interpret about the potential function and mechanism of miR-329 in pancreatic cancer cells. Methods: qRT-PCR was performed to determine the expression level of miR-329 and its target gene in pancreatic cancer tissues and cell lines. Patients' survival was analyzed with the Kaplan-Meier method. Correlation between miR-329 and clinicopathological characteristics were determined by the Pearson c2 test. Mimic was employed to upregulate miR-329 expression. Biological function of miR-329 was examined by cell growth assay, plate clone formation assay and apoptosis analysis in vitro and xenograft tumor growth assay in vivo. Primary pancreatic cancer cells were cultured to further validate its function. Bioinformatic analysis was applied to seek the target gene of miR-329. Target gene was finally identified by luciferase activity assay and western blot. Results: MiR-329 expression was significantly downregulated in pancreatic cancer tissues when compared with paired normal tissues.
* Corresponding authors. These authors contributed equally to this work.
#
Abstract Objective: The aim of this study was to evaluate the diagnostic accuracy of drain/plasma pancreatic amylase values on postoperative day 1 (DPA1/PPA1) in POPF by means of a systemic review and meta-analysis. Methods: Online journal databases and a manual search up to April 2015 were used. Studies clearly documenting DPA1 or PPA1 in predicting overall POPF (Grade 0 vs AþBþC) or clinically relevant POPF (Grade 0þA vs BþC) following pancreatic surgery were selected. Pooled predictive parameters were performed using STATA 12.0. Results: 15 studies were finally identified with a total of 4331 patients. Pooled sensitivity and specificity of DPA1 were 0.92 (95% CI 0.81-0.96) and 0.77 (95% CI 0.64-0.86) for predicting overall POPF and 0.79 (95% CI 0.610.90) and 0.83 (95% CI 0.74-0.89) for predicting clinically relevant POPF. The pooled sensitivity and specificity of PPA1 were 0.74 (95% CI 0.63-0.82) and 0.62 (95% CI 0.55-0.70) for POPF. After the DPA1 at/over cutoff values for overall POPF or clinically relevant POPF, corresponding post-test probability (Post-test (þ)) (if pre-test probability was 50%) was 80% and 82% respectively, while, if values were below the cutoff values, the posttest probability (Post-test (-)) was 10% and 20% respectively. Pveost-test (þ) and Post-test (-) of PPA1 for overall POPF were 66% and 30% respectily. Conclusion: DPA1 is a useful predictive test for overall POPF and clinically relevant POPF which has good sensitivity and specificity based on the current studies. Meanwhile, it should be cautiously applied to clinical practice because cutoffs had a wide range between studies. Keywords: Pancreatic resection; Early drain removal; Drain amylase; Serum amylase; Pancreatic fistula
15288. Artery-first approach pancreaticoduodenectomy with extended retroperitoneal clearence (AFPD-ERC) K. Jiang, J. Wu, W. Gao, J. Chen, J. Wei, F. Guo, Z. Lu, P. Wu, Y. Miao Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
* Corresponding authors. 1 These authors contributed equally to this work.