Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT

 描述（由申请人提供）：全胰腺切除术联合胰岛自体移植（TPIAT）用于治疗药物或内窥镜治疗失败的慢性胰腺炎患者的严重顽固性疼痛。TP缓解了内脏疼痛的来源，而IAT组分降低了术后糖尿病的风险或严重程度。尽管在过去的十年中越来越多的中心提供TPIAT，但关于候选人的选择，结果和干预时机的基本问题仍然存在。2014年7月，该领域的专家参加了由国家荒漠化与发展研究所主办的讲习班，以确定优先研究领域。确定的关键研究差距包括更好地定义用于选择患者的术前措施，制定确定干预时机的指标，开发TPIAT疗效的预测模型，以及测量TPIAT的成本效益。我们建议开展一项TPIAT的多中心前瞻性观察性队列研究，以直接解决这些研究空白。虽然主要目的是确定哪些因素预测衰弱性疼痛的成功解决，但重要的是要考虑糖尿病的风险和手术的成本效益，因为每个因素都可能影响手术的利用。拟议研究的主要目的是确定哪些患者和疾病特征与疼痛的良好缓解和健康相关生活质量的改善相关，并确定手术的最佳时机。次要目的是确定哪些患者和疾病特征预测术后糖尿病的成功解决;并测量TPIAT与正在进行的药物（非TPIAT）管理相比的成本效益。后两个组成部分很重要，因为它们影响TPIAT作为患者和提供者治疗选择的可接受性。为了实现这些目标，我们将在美国8个中心招募450名所有年龄段的TPIAT接受者进行这项专门的手术。患者将在术前、术后6个月、1年和每年接受仔细评估，以描述关键健康特征、心理社会共病、疼痛特征、健康相关生活质量、住院和糖尿病 结果。由于非内脏疼痛，包括中枢致敏，越来越多地被认为是“胰腺”疼痛的重要组成部分，可能不会对手术干预作出最佳反应，我们将在一个单一的中心使用专门的定量感觉测试（QST）评估75例患者的中枢致敏。将采集血液、尿液和胰腺组织病理学样本用于生物储存库，以支持该人群的未来辅助研究。

 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.