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Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models
Mohamed Saleh, … , Krishna Prasadan, George K. Gittes
Mohamed Saleh, … , Krishna Prasadan, George K. Gittes
Published December 22, 2020
Citation Information: J Clin Invest. 2021;131(3):e143301. https://doi.org/10.1172/JCI143301.
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Research Article Endocrinology Gastroenterology

Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models

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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.

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

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Figure 1

Morphological and histological changes in mouse pancreas following chemical pancreatectomy.

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Morphological and histological changes in mouse pancreas following chemi...
(A) After AcA infusion, gross morphology of the pancreas was abnormally white and edematous at 2 days, translucent with visible islets (arrow) at 2 weeks, and replaced by fatty tissue with visible islets (arrow) at 8 weeks. (B and C) Normal pancreas histology 2 days after saline infusion (B). Two days after AcA infusion, there was exocrine tissue necrosis (asterisks) with intact islets (i). Magnification (inset) of the apparently preserved acinar cells revealed cell swelling and cytoplasmic vacuolization (arrows) (C). (D) Histology of the pancreas after AcA infusion. Intact islets are denoted by i. Arrows denote fat cells at 4 weeks. (E) Immunostaining after AcA infusion showed negative amylase staining (arrows denote amylase remnants at 2 days), with normal insulin and glucagon staining. Illustrative histology results from 5 animals per time point are shown. Scale bars: 200 μm.

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