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Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models
Authors:Mohamed Saleh  Kartikeya Sharma  Ranjeet Kalsi  Joseph Fusco  Anuradha Sehrawat  Jami L Saloman  Ping Guo  Ting Zhang  Nada Mohamed  Yan Wang  Krishna Prasadan  George K Gittes
Institution:1.Division of Pediatric Surgery.;2.Division of Pediatric Endocrinology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.;3.Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.;4.Department of Clinical Science, Colorado State University, Fort Collins, Colorado, USA.
Abstract: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.
Keywords:Endocrinology  Gastroenterology
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