Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT



 DESCRIPTION (provided by applicant): Total pancreatectomy with islet autotransplant (TPIAT) is performed to treat the severe, intractable pain of chronic pancreatitis for those patients who have failed medical or endoscopic therapies. The TP relieves the source of visceral pain, while the IAT component reduces the risk for or severity of post-operative diabetes. Despite an increasing number of centers offering TPIAT over the past decade, fundamental questions remain regarding the selection of candidates, outcomes, and timing of intervention. Experts in the field convened at a workshop sponsored by the NIDDK in July 2014 to identify priority areas for research. Key research gaps identified included better defining preoperative measures used to select patients, development of metrics to determine timing of intervention, development of predictive models for efficacy of TPIAT, and measurement of the cost-effectiveness of TPIAT. We propose to conduct a multi-center prospective observational cohort study of TPIAT to directly address these research gaps. While the primary objective is to determine what factors predict successful resolution of debilitating pain, it is important to consider the risk of diabetes and cost- effectiveness of the procedure, as each may impact utilization of surgery. The primary aim of the proposed study is to determine which patient and disease characteristics are associated with favorable resolution of pain and improved health related quality of life, and to determine optimal timing of the procedure. The secondary aims are to determine which patient and disease characteristics predict successful resolution of post-operative diabetes; and to measure the cost-effectiveness of TPIAT compared to ongoing medical (non-TPIAT) management. These latter two components are important because they impact the acceptability of TPIAT as a treatment option for patients and providers. To address these aims, we will enroll 450 TPIAT recipients of all ages, across 8 U.S. centers performing this specialized procedure. Patients will undergo careful assessments before surgery, and at 6 months, 1 year, and yearly after surgery, to describe key health characteristics, psychosocial comorbidities, pain characteristics, health related quality of life, hospitalizations, and diabetes outcomes. Because non-visceral pain, including central sensitization, is increasingly recognized as an important component of "pancreatic" pain that may not respond optimally to surgical intervention, we will assess central sensitization in a subset of 75 patients at a single center using specialized quantitative sensory testing (QST). Samples for blood, urine, and pancreatic histopathology will be collected for a biorepository to support future ancillary studies in this population.