Maruya Yasuhiro, Akazawa Yuko, Norimatsu Kiyuu, Sailaubekova Yerkezhan, Zhumagazhiyeva Nazigul, Kobayashi Shinichiro, Higashi Miki, Hashiguchi Keiichi, Yamaguchi Naoyuki, Nakashima Masahiro, Nakao Kazuhiko, Kanetaka Kengo, Eguchi Susumu
Tissue Engineering and Regenerative Therapeutics in Gastrointestinal Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Regen Ther. 2024 Aug 10;26:557-563. doi: 10.1016/j.reth.2024.08.007. eCollection 2024 Jun.
Autologous oral mucosal epithelial cell sheet (AOMECS) transplantation has recently been applied in human patients to prevent postprocedural stenosis following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma. However, the long-term safety of AOMECS transplantation remains unclear. We evaluated the long-term outcomes of 10 patients who participated in a clinical trial of AOMECS transplantation after esophageal ESD. Additionally, we assessed the local DNA damage response in the esophageal epithelium using p53 binding protein 1 (53BP1) immunofluorescence in post-AOMECS biopsy specimens. The median follow-up period was 118.5 months (range: 46-130 months). Two patients developed primary esophageal cancer near the AOMECS site and successfully underwent additional ESD. One patient developed lymph node metastasis and underwent chemotherapy. None of the patients died from the original disease, although one patient died from unrelated causes. The rate of abnormal 53BP1 nuclear foci, indicative of increased genome instability, increased with the progression of neoplasia in patients post AOMECS. Our case series suggests that AOMECS transplantation provides an acceptable long-term prognosis and 53BP1 foci may serve as a useful marker for assessing DNA instability in the post-AOMECS esophageal epithelium.
自体口腔黏膜上皮细胞片(AOMECS)移植最近已应用于人类患者,以预防食管鳞状细胞癌内镜黏膜下剥离术(ESD)后程序性狭窄。然而,AOMECS移植的长期安全性仍不明确。我们评估了10例参与食管ESD后AOMECS移植临床试验患者的长期结局。此外,我们在AOMECS后活检标本中使用p53结合蛋白1(53BP1)免疫荧光评估食管上皮中的局部DNA损伤反应。中位随访期为118.5个月(范围:46 - 130个月)。两名患者在AOMECS部位附近发生原发性食管癌,并成功接受了额外的ESD。一名患者发生淋巴结转移并接受了化疗。尽管有一名患者死于无关原因,但没有患者死于原发病。AOMECS后患者中,指示基因组不稳定性增加的异常53BP1核灶率随肿瘤进展而增加。我们的病例系列表明,AOMECS移植提供了可接受的长期预后,并且53BP1灶可能作为评估AOMECS后食管上皮DNA不稳定性的有用标志物。