Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT

 描述(申请人提供)：全胰腺切除加胰岛自体移植(TPIAT)是为那些内科或内窥镜治疗失败的患者治疗慢性胰腺炎的严重、顽固性疼痛而进行的。TP可缓解内脏疼痛，而IAT成分可降低术后糖尿病的风险或严重程度。尽管在过去十年中越来越多的中心提供TPIAT，但关于候选人的选择、结果和干预时机的根本问题仍然存在。该领域的专家于2014年7月在NIDDK赞助的一个研讨会上召开会议，以确定研究的优先领域。确定的关键研究差距包括更好地确定用于选择患者的术前措施、制定确定干预时机的指标、开发预测TPIAT疗效的模型以及衡量TPIAT的成本效益。我们建议对TPIAT进行一项多中心前瞻性观察队列研究，以直接解决这些研究空白。虽然主要目标是确定哪些因素预测衰弱疼痛的成功解决，但重要的是要考虑糖尿病的风险和手术的成本效益，因为每种因素都可能影响手术的利用率。这项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与健康相关的生活质量的改善有关，并确定手术的最佳时机。第二个目标是确定哪些患者和疾病特征可以预测手术后糖尿病的成功解决；并衡量与正在进行的内科(非TPIAT)治疗相比，TPIAT的成本效益。后两个部分很重要，因为它们影响了TPIAT作为患者和提供者的治疗选择的可接受性。为了实现这些目标，我们将在8个美国中心招募450名各个年龄段的TPIAT接受者，进行这一专门的程序。患者将在手术前、术后6个月、1年和每年进行仔细的评估，以描述关键的健康特征、心理社会合并症、疼痛特征、与健康相关的生活质量、住院和糖尿病。 结果。由于包括中枢敏感化在内的非内脏疼痛越来越被认为是“胰腺”疼痛的一个重要组成部分，对手术干预的反应可能不是最佳的，因此我们将使用专门的定量感觉测试(QST)评估单个中心的75名患者的中枢敏感化反应。血液、尿液和胰腺组织病理学的样本将被收集用于生物储存库，以支持未来在该人群中的辅助研究。

 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.