CX601, Allogeneic Expanded Adipose-Derived Mesenchymal Stem Cells (EASC), for Complex Perianal Fistulas in Crohn's Disease: Long-Term Results from a Phase III Randomized Controlled Trial

Introduction: Pancreatic cancer is the third leading cause of cancer related death trailing only behind lung and colon cancer.The prognosis for patients diagnosed with pancreatic cancer remains poor with an estimated 5-year survival rate of 7.2%.It has been suggested that statins may inhibit tumor growth by stimulating apoptosis, inhibiting angiogenesis, and suppressing metastatic invasion.Given the dismal prognoses associated with pancreatic cancer and the widely accepted tolerability of statins, the aim of this meta-analysis was to examine if the use of statin therapy leads to increased overall survival in patients diagnosed with pancreatic cancer.Methods: A comprehensive evaluation of all eligible studies was identified by systematically searching the electronic databases PubMed, EMBASE and Cochrane.A total of 230 studies were initially identified, of which four were ultimately included in the meta-analysis.The quality of the studies was assessed and graded by two reviewers independently.The primary endpoint of interest was overall survival assessed by hazard ratio.The pooled hazard ratio (HR) and 95% confidence intervals (CI) were calculated from the original study data by using the Mantel-Haenszel method (fixed effects model).Statistical heterogeneity was assessed using the forest plot and inconsistency statistic (I-squared).If any heterogeneity existed (I-squared > 50%), it was to be explored by subgroup analyses, meta-regression and sensitivity analyses.Results: A total of four retrospective cohort studies, involving 8334 patients diagnosed with pancreatic cancer across eight separate treatment arms, were included.Mean age was 67 years old and 57% were males.Administration of statins to patients with pancreatic cancer increased overall survival by 10% (HR 0.90, 95% Cl 0.852-0.948P-value < 0.001).A high degree of heterogeneity (I-squared 77%) was detected from this primary analysis.It was subsequently noted that a large proportion of the primary analysis came from a single study (Jeon 2015) -which was different from the other studies in several crucial ways.A sensitivity analysis was thus performed -in which the rest of the study arms were separated from the much larger one (which actually contained five separate treatment arms) -in which heterogeneity was dramatically reduced and a statistically significant effect size was maintained.Conclusions: Statin use is associated with increased overall survival in patients diagnosed with pancreatic cancer.Further randomized double-blinded studies should be conducted to confirm the results.