Kalsi Ranjeet S, Kreger Alexander M, Saleh Mohamed, Yoshida Shiho, Sharma Kartikeya, Fusco Joseph, Saloman Jami L, Zhang Ting, Thomas Madison, Sehrawat Anuradha, Wang Yan, Reif Jason, Mills Juliana, Raad Sarah, Zengin Bugra, Gomez Ana, Singhi Aatur, Tadros Sameh, Slivka Adam, Esni Farzad, Prasadan Krishna, Gittes George
UPMC Children's Hospital of Pittsburgh.
University of Pittsburgh School of Medicine.
Res Sq. 2023 Mar 8:rs.3.rs-2618133. doi: 10.21203/rs.3.rs-2618133/v1.
Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that "chemical pancreatectomy," a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.
慢性胰腺炎是一种使人衰弱的疾病，影响着全球数百万人。这些患者遭受剧烈疼痛的发作，止痛药物只能轻微缓解疼痛，可能需要进行具有高发病率和死亡率的大型手术。此前，我们证明了“化学性胰腺切除术”，即胰腺导管内注入稀醋酸溶液，可切除外分泌胰腺，同时保留内分泌胰腺。值得注意的是，化学性胰腺切除术可解决慢性炎症，减轻雨蛙肽胰腺炎模型中的异常性疼痛，并改善葡萄糖稳态。在此，我们广泛测试了化学性胰腺切除术在非人灵长类动物中的可行性，并验证了我们之前发表的初步研究。我们对腹部和骨盆进行了系列计算机断层扫描（CT），分析了背根神经节，测量了血清酶，并进行了组织学和超微结构评估以及胰腺内分泌功能测定。基于系列CT扫描，化学性胰腺切除术导致胰腺体积减小。免疫组织化学和透射电子显微镜显示外分泌胰腺被切除，内分泌胰岛得以保留。重要的是，化学性胰腺切除术并未增加所采集背根神经节中的伤害性感受标记物。此外，化学性胰腺切除术在体内和体外均将胰岛素分泌提高到超常水平。因此，本研究可能为将该手术应用于慢性胰腺炎患者或其他需要进行胰腺切除术的疾病患者提供基础。
