SPINK1 and pancreatic neoplasm: In this model, SPINK1-regulated pathways would include all upstream etiologic factors associated with recurrent trypsinogen activation (e.g. PRSS1 and CFTR mutations) while SPINK1-independent pathways would include factors that drive PSC to produce fibrosis through mechanisms that are generally independent of recurrent trypsinogen activation (e.g. autoimmune pancreatitis, toxins, pancreatic cancer).