Background: Pancreatic fistula is one of the main complications after pancreatic surgery and the leading cause of morbidity and mortality after pancreatic surgery. There are many pieces of evidence emerging out from retrospective studies and metanalysis that neoadjuvant chemoradiation decreases rates of clinically significant postoperative pancreatic fistula. Aims and objectives: The primary aim of our analysis was to do a systemic review and updated meta-analysis of literature published in the last 10 years and look for the association of neoadjuvant chemoradiation and risk of subsequent clinically significant pancreatic fistula. Methods: EMBASE, MEDLINE, and the Cochrane Database were searched for Studies comparing outcomes in patients receiving neoadjuvant chemoradiotherapy first with those patients who received surgery first in case of pancreatic cancer. A systemic review and Metanalysis were done according to MOOSE and PRISMA guidelines. Heterogeneity was measured using Q tests and I2, and p < 0.10 was determined as significant. The Odds ratios (OR) and Risk Ratios (RR) were calculated for dichotomous data as per the requirement, and weighted mean differences (WMD) were used for continuous variables. Nonrandomized trials were accessed for bias using the New Castle Ottawa scale. Publication bias was studied using funnel plots. The meta-analysis was conducted using Open Review Manager 5.4. Results: Twenty-six studies including 17021 patients finally included in the analysis. 339 patients out of a total of 3386 developed clinically significant pancreatic fistula in the neoadjuvant first group. 2342 patients out of 13335 patients developed clinically significant pancreatic fistula in the surgery first group. Neoadjuvant treatment significantly reduced the risk of subsequent clinically significant pancreatic fistula. (p= <0.0001). The number of patients with soft pancreas was significantly higher in the surgery first group. (p <0.0001). Pancreatic duct diameter mentioned in only two studies but there was no significant difference between both groups. [p=1].Blood loss was significantly more in the surgery first group.[ p <0.0001]. There was no difference in pancreaticoduodenectomy or distal pancreatectomy performed between both groups. (p=0.82). There was no difference in the number of borderline resectable pancreatic tumors between both groups. (p= 0.34). There was no difference in overall grade 3/grade 4 complications rate between both groups. (p= 0.39). Conclusion: Neoadjuvant treatments may be responsible for the lower rates of clinically significant pancreatic fistula after subsequent surgery.
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