The Clinical Study And Meta-analysis Of Laparoscopic Distal Pancreatectomy

In1996, Cuschieri reported the first case of laparoscopic distal pancreatectomy (LDP) which had significant advantages of minimally invasion with small incision, light pain and rapid recovery. Thence the literatures reported were gradually increasing, but there were a notable difference between the results reported in the literature, paticularly lacking the comparative studies with open distal pancreatectomy (Open Distal Pancreatectomy, ODP), a meta-analysis of high quality observational studies were performed in order to evaluate the status of LDP. Furthermore, in order to sum up the experience on LDP, a retrospective study was performed comparing LDP with ODP performed in our hospital from December2003to May2011.Part1:Clinical study on laparoscopic distal pancreatectomy comparing with open distal pancreatectomyObjective:1. To investigate the safety and feasibility of LDP.2. To evaluate the advantages and disadvantages of LDP comparing with ODP in the postoperative pain, postoperative recovery and postoperative morbidity.Methods:From December2003to May2011, the patients who suffer distal pancreatic diseases in our institution were included in this study. The analysis indicators included: the operation time, blood loss, postoperative first flatus time, the intake time, postoperative hospital stay, postoperative morbidity, hospital charges and follow-up conditions. In addition, all patients were divided into the Early Group (2003-2005), the Medium Group (2006-2008) and the Late Group (2009-present).The operative time, blood loss, postoperative hospital stay and postoperative morbidity between the three groups were compared to analyze the impact of the surgical experience on the LDP.Results:Totally,170cases were included in this study, with69cases in LDP group and91cases in ODP group. There were no significant differences with sex, age, BMI and ASA status between the two groups. The operation time was similar between the two groups, but the LDP group was associated with less blood loss (183.56±120.34ml vs382.4±144.6ml, P<0.05). Patients in the LDP group recovered faster:first flatus, first liquid diet and postoperative hospital stay were significantly shorter than those in the ODP group. Moreover, the LDP group had lower VAS scores (1.9±0.6vs.2.6±0.6, P=0.027) and less analgesics (20.7±11.6vs.55.6±30.2, P<0.001). The postoperative morbidity of LDP were significantly lower than the ODP group (17.4%vs.31.8%, P <0.05), while the incidence of pancreatic fistula was no significant statistical difference (11.6%vs.18.6%, P=0.221).There were no significant differences of BUN and CR between these two groups at all measurement points (1d,3d,5d, postoperatively). ALT of1d,3d and5d of LDP group were significantly lower than the ODP group and ALB of1d,3d and5d of LDP group were significantly higher in the ODP group. The numbers of WBC at all measurement points and NE of1d and5d postoperatively were significantly lower in the LDP groupThe total charges of the LDP group were higher than the ODP group (41721±9130CNY vs36108±11132CNY, P=0.042), mainly the operation charges of LDP group were significantly higher than the ODP group (23310±3203CNY vs.16156±4026CNY, P=0.033). But the drug charges of LDP group were lower than the ODP group (15104±3574CNY vs.16991±5113CNY, p=0.041). In subgroup analysis, the overall charges of the Early group (2003-2005) and Medium group (2006-2008) were higher than the ODP group, but the Late group (2009-present) has no significant difference.In LDP subgroup analysis, the operative time of Combined group (the patients received combined resection of other organ) were longer than that of the No-Combined group, while there were no significant differences in blood loss, first flatus, first intake time and postoperative hospital stay between the two groups. In addition, comparing with open distal pancreatectomy, the spleen-preserving subgroup (who received spleen-preserving distal pancreatectomy) had no significant differences in operation time, blood loss, first flatus, first intake time and postoperative hospital stay.About the learning curve of LDP, The operative time, blood loss and postoperative hospital stay of the Late group were significantly lower than that in the Early group, while postoperative morbidity were no significant difference among the three groups.Conclusion:1. LDP is a procedure as safe and feasible as ODP.2. LDP has obvious mini-invasive advantages, such as accelerating the postoperative recovery, alleviating the postoperative pain and the overall postoperative morbidity.3. Surgeons who reached the learning curve of40cases could better perform the advantages of the LDP.Part2:Laparoscopic distal pancreatectomy is as safe and feasible as open procedure:A meta-analysisObjective:To evaluate the feasibility and safety of laparoscopic distal pancreatectomy (LDP) compared with open distal pancreatectomy (ODP) with a EBM (evidence based medicine) Meta-analysisMethods:Meta-analysis was performed using the databases, including Pubmed, the Cochrane Central Register of Controlled Trials, Web of Science and BIOSIS Previews. Articles should contain quantitative data of the comparison of LDP and ODP. Each article was reviewed by two authors. Indices of operative time, spleen-preserving rate, time to fluid intake, ratio of malignant tumors, postoperative hospital stay, the incidence rate of pancreatic fistula and overall morbidity rate were analyzed.Results:Nine articles with1341patients who underwent pancreatectomy met the inclusion criteria. LDP was performed in501(37.4%) patients, while ODP was performed in840(62.6%) patients. There were significant differences in the operative time, time to fluid intake, postoperative hospital stay and spleen-preserving rate between LDP and ODP. There was no difference between the two groups in pancreatic fistula rate [random effects model. RR0.996(0.663,1.494), P=0.983,I2=28.4%] and overall morbidity rate [random effects model, RR0.81(0.596,1.101). P=0.178,I-=55.6%].Conclusions:LDP has the advantages of shorter hospital stay and operative time, more rapid recovery and higher spleen-preserving rate as compared with ODP.Part3:The impact of epithelial mesenchymal transition mediated by HIF-la/Notch signaling on pancreatic cancer stem cellObjective:To clarify the impact and the mechanism of EMT mediated by HIF-la/Notch signal pathway in the maintaining the properties of pancreatic cancer stem cell.Methods:RNAi vector was designed according to HIF-1α gene sequence. The expressions of HIF-1α, E-Cad, N-Cad, Notchl and snail were detected by Real time RT-PCR and Western blot among vector transfected cells, hypoxia induced cells and normal cells. Proliferative activity was detected by MTT and the pancreatic cancer stem cell ratios were detected by flow cytometry.Results:HIF-la vector was successfully constructed and the best transfection rate was86.5%. The expressions of notchl (19.3±0.6vs.66.7±0.6, P<0.001), N-Cad (0.5±0.2vs.15.10±0.7, P<0.001), snai(2.9±0.5vs.4.4±0.2, P=0.021)significantly decreased and E-cadherin (2.6±0.9vs.0.6±0.27, P<0.001) expression significantly increased. In hypoxia induced group, the results showed that the expressions of notchl (16.5±0.8vs.53.4±0.6, P<0.001),N-Cad (20.3±1.1vs.27.4±1.6, P<0.001), snail (2.4±0.0vs.3.9±0.9,P=0.038) significantly increased and E-cadherin expression significantly decreased (2.9±0.16vs.0.7±0.2, P<0.001). Flow cytometry results showed that CD44+expression rate was91.72%±2.26%and CD24+expression rate was5.53%in the normal MIA-PaCa2cell lines. In vector tranfected group, CD44+expression rate significantly decreased (83.08±3.43%, P<0.05) and CD24+expression rate significantly increased (14.41%±5.28%, p<0.01). In hypoxia induced group, CD44+expression rate significantly increased (95.54%±2.37%, P<0.05), CD24+expression rate significantly decreased (3.21%±0.78%, P<0.05). MTT assay results showed that proliferative activity was significantly inhibited after transfected.Conclusions:1. The inhibition of HIF-1α could reduce EMT and the proliferation of pancreatic cancer MIA-PaCa2cell line, showing that the regulation of HIF-1α/Notch pathway could affect EMT of pancreatic cancer MIA-PaCa2cell by changing the expressions of notchl, N-Cad, snail and E-cadherin gene.2. Some cells of MIA-PaCa2could convert to cancer stem cells after obtaining EMT ability, and the inhibition of EMT could reduce the ratios of pancreatic cancer stem cell, showing that EMT was a necessary process for MIA-PaCa2cell to transform to cancer stem cell.