Takebayashi Katsushi, Murata Satoshi, Kodama Hirokazu, Kaida Sachiko, Yamaguchi Tsuyoshi, Ishikawa Ken, Shimoji Miyuki, Miyake Toru, Ueki Tomoyuki, Kojima Masatsugu, Iida Hiroya, Maehira Hiromitsu, Shimizu Tomoharu, Tani Masaji
Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan; Cancer Center, Shiga University of Medical Science Hospital, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Eur J Surg Oncol. 2022 Jan;48(1):177-182. doi: 10.1016/j.ejso.2021.05.012. Epub 2021 May 20.
Cancer cells in intraoperative peritoneal washings (PW) indicate increased peritoneal recurrence. Detection of CEA or CK20 genes indicates poor prognosis. We assessed long-term prognosis of patients with amplification of cancer-related genes in PW obtained intraoperatively during curative gastric cancer surgery.
PW was collected before and immediately after curative gastrectomy. CEA, CK20, TFF1, MUC2, and FABP1-mRNA were selected as marker genes for reverse transcription polymerase chain reaction. Peritoneal recurrence-free survival (PRFS) and overall survival (OS) after >7-year follow-up were examined using the Kaplan-Meier method.
Of 138 patients who underwent gastrectomy with negative cytological findings at laparotomy, 80 patients showed negative cancer-related gene amplification in preoperative PW. Fifty-eight patients were excluded due to positive gene amplification, which suggested presence of preoperative peritoneal cancer cells. The 80 patients had mRNA amplification in PW after surgery. Amplification of multiple and single cancer-related marker genes was observed in 38 and 21 patients; 21 cases had marker-negative results. Five-year PRFS was 69.1%, 95.2%, and 100% in multi-marker-positive, single marker-positive, and marker-negative cases, respectively. Multi-marker-positive patients had significantly worse PRFS than the other groups (p < 0.05). Multivariate analysis in the Cox proportional hazards model identified multi-marker-positivity as an independent prognostic factor for PRFS (hazard ratio, 7.6; 95% confidence interval, 1.07-62.63; p = 0.046), and multi-marker-positive patients had significantly worse OS than other groups (p < 0.01).
Multi-marker cancer-related gene amplification in PW is associated with worse prognosis in PRFS and OS even after a long follow-up; PRFS can be stratified by the number of genes amplified.
术中腹腔冲洗液（PW）中的癌细胞提示腹腔复发增加。检测癌胚抗原（CEA）或细胞角蛋白20（CK20）基因提示预后不良。我们评估了在胃癌根治性手术中术中获取的PW中癌症相关基因扩增患者的长期预后。
在根治性胃切除术前及术后立即收集PW。选择CEA、CK20、三叶因子1（TFF1）、黏蛋白2（MUC2）和脂肪酸结合蛋白1（FABP1）-mRNA作为逆转录聚合酶链反应的标记基因。采用Kaplan-Meier法检查>7年随访后的无腹膜复发生存期（PRFS）和总生存期（OS）。
138例行剖腹探查细胞学检查阴性的胃切除患者中，80例术前PW中癌症相关基因扩增阴性。58例因基因扩增阳性而被排除，这提示术前存在腹腔癌细胞。80例患者术后PW中有mRNA扩增。38例和21例患者分别观察到多个和单个癌症相关标记基因的扩增；21例标记结果为阴性。多标记阳性、单标记阳性和标记阴性病例的5年PRFS分别为69.1%、95.2%和100%。多标记阳性患者的PRFS明显差于其他组（p<0.05）。Cox比例风险模型的多因素分析确定多标记阳性是PRFS的独立预后因素（风险比，7.6；95%置信区间，1.07-62.63；p=0.046），多标记阳性患者的OS明显差于其他组（p<0.01）。
PW中多标记癌症相关基因扩增与PRFS和OS的较差预后相关，即使经过长期随访；PRFS可根据扩增基因的数量进行分层。
