Asano Kosho, Mikata Rintaro, Chiba Tetsuhiro, Kan Motoyasu, Maruta Shikiko, Yamada Toshihito, Miura Yoshifumi, Shima Yukiko, Sensui Miyuki, Nagashima Hiroki, Yokoyama Masayuki, Ohyama Hiroshi, Kusakabe Yuko, Yasui Shin, Sugiyama Harutoshi, Ohno Izumi, Kato Jun, Takano Shigetsugu, Ohtsuka Masayuki, Kato Naoya
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Pancreatology. 2021 Apr 15. doi: 10.1016/j.pan.2021.04.001.
BACKGROUND/OBJECTIVES: Recently, increase in cell-free DNA (cfDNA) concentration or newly detected KRAS mutation after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy were reported to be related to the occurrence of new distant metastasis. In this study, we investigated whether cfDNA concentration increased with the release of tumor components into the blood after EUS-FNA and whether its increase was related to prognosis.
Sixty-eight patients underwent EUS-FNA and were pathologically confirmed as having pancreatic ductal adenocarcinoma (PDAC). We measured plasma cfDNA concentration and the copy number of KRAS mutation in 68 patients and circulating tumor cells in 8 before and after EUS-FNA.
The average cfDNA concentration after EUS-FNA (672.5 ± 919.6 ng/mL) was significantly higher than that before EUS-FNA (527.7 ± 827.3 ng/mL) (P < 0.001). KRAS mutation in plasma was detected in 8 patients (11.8%), however a significant increase in cfDNA concentration after EUS-FNA was not related to the change in KRAS-mutant copy number. Minimal increase in circulating tumor cells was observed in 3 of 8 patients. New distant metastasis was observed within 286 days to initial metastasis detection in 6 of 12 patients with ≥2-fold increase in cfDNA concentration and 26 of 56 patients with <2-fold increase within 185 days. In 32 patients who underwent surgery, ≥2-fold increase in cfDNA did not affect early recurrence.
The increase in cfDNA concentration after EUS-FNA was not caused by tumor cell components released into blood vessels. Hence, the risk of seeding via the blood stream after EUS-FNA may need not be considered.
背景/目的：最近，有报道称内镜超声引导下细针穿刺活检（EUS-FNA）后游离DNA（cfDNA）浓度升高或新检测到KRAS突变与新的远处转移的发生有关。在本研究中，我们调查了EUS-FNA后cfDNA浓度是否随着肿瘤成分释放到血液中而增加，以及其增加是否与预后相关。
68例患者接受了EUS-FNA，并经病理证实为胰腺导管腺癌（PDAC）。我们测量了68例患者EUS-FNA前后的血浆cfDNA浓度、KRAS突变拷贝数以及8例患者的循环肿瘤细胞。
EUS-FNA后cfDNA平均浓度（672.5±919.6 ng/mL）显著高于EUS-FNA前（527.7±827.3 ng/mL）（P<0.001）。8例患者（11.8%）血浆中检测到KRAS突变，然而EUS-FNA后cfDNA浓度的显著增加与KRAS突变拷贝数的变化无关。8例患者中有3例观察到循环肿瘤细胞的最小增加。在cfDNA浓度增加≥2倍的12例患者中有6例以及cfDNA浓度增加<2倍的56例患者中有26例在初次转移检测后的286天内观察到新的远处转移。在32例接受手术的患者中，cfDNA增加≥2倍并不影响早期复发。
EUS-FNA后cfDNA浓度的增加不是由释放到血管中的肿瘤细胞成分引起的。因此，可能无需考虑EUS-FNA后通过血流播散的风险。
