Division of Pediatric Surgery.
Division of Pediatric Endocrinology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Clin Invest. 2021 Feb 1;131(3). doi: 10.1172/JCI143301.
Chronic pancreatitis affects over 250,000 people in the US and millions worldwide. It is associated with chronic debilitating pain, pancreatic exocrine failure, and high risk of pancreatic cancer and usually progresses to diabetes. Treatment options are limited and ineffective. We developed a new potential therapy, wherein a pancreatic ductal infusion of 1%-2% acetic acid in mice and nonhuman primates resulted in a nonregenerative, near-complete ablation of the exocrine pancreas, with complete preservation of the islets. Pancreatic ductal infusion of acetic acid in a mouse model of chronic pancreatitis led to resolution of chronic inflammation and pancreatitis-associated pain. Furthermore, acetic acid-treated animals showed improved glucose tolerance and insulin secretion. The loss of exocrine tissue in this procedure would not typically require further management in patients with chronic pancreatitis because they usually have pancreatic exocrine failure requiring dietary enzyme supplements. Thus, this procedure, which should be readily translatable to humans through an endoscopic retrograde cholangiopancreatography (ERCP), may offer a potential innovative nonsurgical therapy for chronic pancreatitis that relieves pain and prevents the progression of pancreatic diabetes.
慢性胰腺炎影响超过 25 万美国人，全球数百万人。它与慢性衰弱性疼痛、胰腺外分泌功能衰竭、胰腺癌高风险相关，通常会进展为糖尿病。治疗选择有限且效果不佳。我们开发了一种新的潜在疗法，在小鼠和非人类灵长类动物中，通过胰腺导管输注 1%-2%的醋酸，导致外分泌胰腺不可再生、近乎完全消融，胰岛完全保留。在慢性胰腺炎的小鼠模型中，胰腺导管内输注醋酸可导致慢性炎症和胰腺炎相关疼痛的缓解。此外，接受醋酸治疗的动物表现出改善的葡萄糖耐量和胰岛素分泌。在这个过程中外分泌组织的丧失通常不需要在慢性胰腺炎患者中进一步管理，因为他们通常患有胰腺外分泌功能衰竭，需要膳食酶补充剂。因此，通过内镜逆行胰胆管造影术（ERCP）可以很容易地将该手术转化为人类，这可能为慢性胰腺炎提供一种有潜力的创新非手术治疗方法，缓解疼痛并防止胰腺糖尿病的进展。
