Whitcomb David C
Cell Biology and Molecular Physiology, and Human Genetics, Division of Gastroenterology, Hepatology and Nutrition (Chief 1999-2016), University of Pittsburgh and UPMC, Pittsburgh, PA, United States.
Ariel Precision Medicine, Pittsburgh, PA, United States.
Front Pediatr. 2022 Aug 15;10:941852. doi: 10.3389/fped.2022.941852. eCollection 2022.
Traditional approaches to understanding the origins of chronic pancreatitis (CP) and find treatments led to abysmal failure. Thus, no drugs now exists to meet this need. Outdated concepts of the etiopathogenesis of CP have been replaced with new insights and disease models that provide the framework for early detection of the pathogenic pancreatitis process. Application of these principals require a new paradigm in disease definition and management, i.e. personalized / precision medicine. The key is acute pancreatitis (AP) starting with the first (sentinel) acute pancreatitis (AP) event (SAPE). This event sensitizes the pancreas to recurrent acute pancreatitis (RAP) as ongoing stressors drive various inflammatory responses to cause CP. The problem is the complex etiologies of AP and the additional genetic and environmental factors that promote progression to RAP and CP. This paper provides a background on the key conceptual changes that facilitate new approaches and the rationale for using mechanism-specific therapies to prevent RAP and CP.
传统上理解慢性胰腺炎（CP）病因并寻找治疗方法的途径遭遇了惨败。因此，目前没有药物能满足这一需求。CP病因发病机制的陈旧概念已被新的见解和疾病模型所取代，这些新见解和疾病模型为早期检测致病性胰腺炎过程提供了框架。应用这些原则需要疾病定义和管理方面的新范式，即个性化/精准医学。关键在于始于首次（哨兵）急性胰腺炎（AP）事件（SAPE）的急性胰腺炎（AP）。该事件使胰腺对复发性急性胰腺炎（RAP）敏感，因为持续的应激源会引发各种炎症反应，进而导致CP。问题在于AP复杂的病因以及促使病情发展为RAP和CP的其他遗传和环境因素。本文提供了有助于新方法的关键概念变化的背景信息，以及使用针对特定机制的疗法预防RAP和CP的基本原理。
