KRAS Mutations in Duodenal Lavage Fluid after Secretin Stimulation for Detection of Pancreatic Cancer
Shinichi Yachida, Shigetaka Yoshinaga, Satoshi Shiba, Makiko Urabe, Hidenori Tanaka, Yohei Takeda, Akinori Shimizu, Yuri Sakamoto, Susumu Hijioka, Shin Haba, Reiko Ashida, Yoshinori Kushiyama, Kento Asano, Makiko Kobayashi, Yoshiyuki Murawaki, Kouji Onishi, Taro Yamashita, Hirokazu Kimura, Yasushi Totoki, Hideki Kamada, Hajime Isomoto, Satoshi Hattori, Chigusa Morizane, Kazuyoshi Ohkawa, Masayuki Kitano, Kazuo Hara, Kenji Ikezawa, Keiji Hanada, Kazuya Matsumoto
Abstract
OBJECTIVE: Although pancreatic ductal adenocarcinoma (PDAC) is still a devastating disease, the survival rate for surgically removed PDACs has significantly improved in recent years. Early detection is essential in managing PDAC. SUMMARY BACKGROUND DATA: The presence of KRAS mutations in PDAC leads to the initial genetic abnormality and offers a significant timeframe for identifying resectable PDACs. A minimally invasive and highly specific PDAC screening test is necessary to prevent the need for invasive follow-up tests. METHODS: Between July 2021 and March 2023, 169 cases were enrolled in 7 institutions. By administering secretin before esophagogastroduodenoscopy (EGD), the excretion of pancreatic juice into the papillary fluid can be stimulated, creating a resource for testing. Washing fluid was collected using a specialized catheter from control individuals (n=75) and patients with resectable PDAC (n=89) at the initial diagnosis. A highly sensitive technique was employed to study KRAS gene mutations. RESULTS: This study obtained an AUC of 0.934 [95%CI: 0.904, 0.964] when using KRAS mutations in duodenal lavage fluid to differentiate between patients with resectable PDAC and healthy controls. The estimated sensitivities were calculated with specificity set at 100%, resulting in a sensitivity of 83.1% [95%CI: 71.7%, 91.2%]. The McNemer test showed a significantly higher sensitivity for KRAS mutations than serum CEA and CA19-9 (P<0.0001). CONCLUSIONS: We created a method to identify resectable PDACs by analyzing KRAS mutation levels in duodenal fluid collected during EGD with secretin stimulation of pancreatic juice secretion.