Table 2.

Factors to be considered in the design of future trials of the endoscopic and surgical treatment of pain in chronic pancreatitis

Factors	Comments
Demography	Variables including age, sex and recurrent acute pancreatitis may influence outcome
Aetiology	Toxic aetiology (alcohol and smoking) predicts a better outcome on pain after surgical resection, although the opposite was found after TPIAT
Imaging features	Parenchymal calcifications have predicted postoperative pain relief in some studies. Patients with strictures and stones in the main pancreatic duct may respond to invasive therapies, but as pathology of the pancreatic duct system is not associated with clinical pain, responders need to be identified
Procedures	Multiple endoscopic procedures may negatively affect outcome
Opioid use	Opioid use has a negative effect on outcome, but represents a bias as the patients typically represent a subgroup with more severe pain, disability and reduced quality of life that predicts a bad outcome to treatment per se
Pain evolution	Long pain duration may affect the outcome in a negative way, but data are subject to selection and recall bias. A temporal association between the development of pancreatic morphological changes and pain may predict a favourable prognosis to invasive treatments
Pain descriptors	Intermittent pain pattern, as opposed to constant pain, may be associated with better outcomes and probably reflects the absence of central sensitisation
Pain assessment	Validated tools for assessment of the multidimensional pain experience, including assessment of physical, psychological and social functioning, are recommended. Catastrophizing and psychological comorbidity to pain also need to be considered. QST may prove useful for objective assessment of pain mechanisms, but requires more validation
Design	Adequately powered studies, well-defined patient cohorts and randomisation are essential. However, without sham-controlled studies, it is not possible to determine non-placebo effect sizes of treatment.

QST, Quantitative sensory testing; TPIAT,  total pancreatectomy with islet autotransplantation.