PMID- 38052736 OWN - NLM STAT- MEDLINE DCOM- 20240208 LR - 20240312 IS - 1534-4681 (Electronic) IS - 1068-9265 (Linking) VI - 31 IP - 3 DP - 2024 Mar TI - Impact of Neutrophil Extracellular Traps Identified by Citrullinated Histone H3 Immunohistochemistry for Postoperative Prognosis in Patients with Extrahepatic Cholangiocarcinomas. PG - 2090-2100 LID - 10.1245/s10434-023-14638-2 [doi] AB - BACKGROUND: Neutrophil extracellular traps (NETs) are extracellular chromatin structures composed of cytoplasmic, granular, and nuclear components of neutrophils. Recently, NETs have received much attention for their role in tumor biology; however, their impact on the postoperative prognosis of patients with extrahepatic cholangiocarcinomas (EHCCs) remains unclear. The purpose of this study was to clarify the impact of NETs identified by immunohistochemical citrullinated histone H3 (Cit-H3) staining on postoperative overall survival (OS) in patients with perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC). METHODS: This study included 318 patients with EHCC (PHCC, n = 192; DCC, n = 126) who underwent surgical resection with curative intent. Neutrophils and NETs were identified by immunohistochemistry using antibodies against CD15 and Cit-H3, respectively. Based on the distribution of CD15 and Cit-H3 expression in the tumor bed, the patients were classified into four groups: one negative group and three subgroups of the positive group (diffuse, intermediate, and focal subgroups). RESULTS: No significant difference was found in the postoperative OS rate depending on the distribution of CD15 expression in patients with PHCC or DCC. However, the three subgroups with positive Cit-H3 expression had significantly poorer OS than the negative group for both PHCC and DCC. Moreover, positive Cit-H3 was an independent OS factor in the multivariable analyses of PHCC (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.11-2.59, P = 0.0115) and DCC (HR 2.03; 95% CI 1.21-3.42, P = 0.0057). CONCLUSIONS: The presence of NETs in the tumor microenvironment may have adverse prognostic effects in patients with EHCCs. CI - (c) 2023. Society of Surgical Oncology. FAU - Yamamoto, Hiroyuki AU - Yamamoto H AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Nakanishi, Yoshitsugu AU - Nakanishi Y AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. y.nakanishi@mac.com. FAU - Mitsuhashi, Tomoko AU - Mitsuhashi T AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Hatanaka, Yutaka AU - Hatanaka Y AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Hatanaka, Kanako AU - Hatanaka K AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Nange, Ayae AU - Nange A AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Yoshida, Yusuke AU - Yoshida Y AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Ino, Norito AU - Ino N AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Go, Masaru AU - Go M AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. AD - Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. FAU - Okamura, Keisuke AU - Okamura K AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Tsuchikawa, Takahiro AU - Tsuchikawa T AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Nakamura, Toru AU - Nakamura T AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Noji, Takehiro AU - Noji T AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Asano, Toshimichi AU - Asano T AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Matsui, Aya AU - Matsui A AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Tanaka, Kimitaka AU - Tanaka K AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Murakami, Soichi AU - Murakami S AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Ebihara, Yuma AU - Ebihara Y AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Kurashima, Yo AU - Kurashima Y AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Shichinohe, Toshiaki AU - Shichinohe T AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. FAU - Hirano, Satoshi AU - Hirano S AD - Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan. LA - eng PT - Journal Article DEP - 20231205 PL - United States TA - Ann Surg Oncol JT - Annals of surgical oncology JID - 9420840 RN - 0 (Histones) SB - IM CIN - Ann Surg Oncol. 2024 Feb;31(2):1272-1273. PMID: 38071713 MH - Humans MH - Histones/metabolism MH - *Extracellular Traps/metabolism MH - Immunohistochemistry MH - *Cholangiocarcinoma/surgery MH - Prognosis MH - Neutrophils/pathology MH - *Klatskin Tumor MH - *Bile Duct Neoplasms/surgery MH - Bile Ducts, Intrahepatic/pathology MH - Tumor Microenvironment EDAT- 2023/12/06 03:43 MHDA- 2024/02/08 06:43 CRDT- 2023/12/05 23:03 PHST- 2023/04/18 00:00 [received] PHST- 2023/11/07 00:00 [accepted] PHST- 2024/02/08 06:43 [medline] PHST- 2023/12/06 03:43 [pubmed] PHST- 2023/12/05 23:03 [entrez] AID - 10.1245/s10434-023-14638-2 [pii] AID - 10.1245/s10434-023-14638-2 [doi] PST - ppublish SO - Ann Surg Oncol. 2024 Mar;31(3):2090-2100. doi: 10.1245/s10434-023-14638-2. Epub 2023 Dec 5.