Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
Ann Surg. 2009 Dec;250(6):878-87. doi: 10.1097/SLA.0b013e3181b21c7b.
To test the hypothesis that signet ring cell (SRC) histology has a negative prognostic value in patients with gastric adenocarcinoma (ADC).
In western countries, gastric ADC with SRC often occurs after the disease has advanced. Consequently, the prognosis of SRC is generally regarded as poor, although survival studies comparing SRC and non-SRC have yielded inconsistent results.
: An intent to treat analysis was performed among 215 patients with gastric ADC scheduled for surgical resection from 1996 to 2007. Of these, 180 patients underwent the resection and 35 were not resected due to diffuse metastatic illness. From 59 resected patients with SRC (SRC group), control non-SRC resected patients matched by age, gender, American Society of Anaesthesiologists (ASA) classification, tumoral location, and pTNM stage were randomly selected by computer (non-SRC group: n = 100) during the same study period.
The overall median survival was 21 months, which was significantly higher in resected compared to non-resected patients (31 vs. 5 months, P < 0.001). In non-resected patients, SRC histological subtype was associated with higher rates of diffuse peritoneal carcinomatosis (90.1% vs. 62.5%, P = 0.053) and neoplastic ascitis (63.6% vs. 34.7%, P = 0.059) and poorer median survival (5 vs. 7 months, P = 0.062). For resected patients, the 2 groups (SRC and non-SRC) were comparable regarding matching variables, demographic variables, and postoperative course. The median survival was significantly lower for SRC patients (21 vs. 44 months, P = 0.004). SRC resected patients exhibited higher rates of localized peritoneal carcinomatosis (P = 0.013) and lymph node involvement (P < 0.001) at diagnosis, lower R0 resection rate (P = 0.019) and earlier tumor relapse (P = 0.009), which was generally in a peritoneal carcinomatosis form (P = 0.011). By multivariate analysis, we concluded that SRC histology was independently associated with a dismal prognosis after adjustment on confounding variables (hazard ratio = 1.5, 95% confidence interval 1.1-2.0, P = 0.004). The prognostic role of SRC was maintained after exclusion of patients with advanced stage at initial diagnosis such as localized peritoneal carcinomatosis or lymph node invasion.
This study is currently the best evidence showing that SRC is a major and independent predictor of poor prognosis due to specific characteristics such as more infiltrating tumors showing affinity for lymphatic tissue accompanied by a higher rate of peritoneal carcinomatosis. Our results suggest the need for a specific therapeutic strategy for such tumors.
检验胃腺癌（ADC）患者中印戒细胞（SRC）组织学具有负预后价值的假设。
在西方国家，SRC 型胃 ADC 通常在疾病进展后发生。因此，SRC 的预后通常被认为较差，尽管比较 SRC 和非-SRC 的生存研究得出了不一致的结果。
对 1996 年至 2007 年期间计划接受手术切除的 215 例胃 ADC 患者进行意向治疗分析。其中，180 例患者接受了切除，35 例因弥漫性转移性疾病未切除。从 59 例 SRC 切除患者（SRC 组）中，通过计算机随机选择年龄、性别、美国麻醉师协会（ASA）分类、肿瘤位置和 pTNM 分期与非-SRC 切除患者相匹配的对照患者（非-SRC 组：n=100））在同一研究期间。
总体中位生存期为 21 个月，切除患者明显高于未切除患者（31 与 5 个月，P<0.001）。在未切除的患者中，SRC 组织学亚型与更高的弥漫性腹膜癌（90.1%与 62.5%，P=0.053）和肿瘤性腹水（63.6%与 34.7%，P=0.059）发生率和较差的中位生存期（5 与 7 个月，P=0.062）相关。对于切除的患者，两组（SRC 和非-SRC）在匹配变量、人口统计学变量和术后过程方面具有可比性。SRC 患者的中位生存期明显更短（21 与 44 个月，P=0.004）。SRC 切除患者在诊断时腹膜癌（P=0.013）和淋巴结受累（P<0.001）的发生率更高，R0 切除率（P=0.019）和肿瘤复发更早（P=0.009），通常为腹膜癌形式（P=0.011）。通过多变量分析，我们得出结论，在调整混杂变量后，SRC 组织学与预后不良独立相关（风险比=1.5，95%置信区间 1.1-2.0，P=0.004）。在排除局部腹膜癌或淋巴结侵犯等初始诊断晚期患者后，SRC 的预后作用仍然存在。
本研究目前是最好的证据，表明 SRC 是预后不良的主要和独立预测因素，这归因于其具有特定特征，例如更具侵袭性的肿瘤，显示出对淋巴组织的亲和力，并伴有更高的腹膜癌发生率。我们的结果表明，需要针对此类肿瘤制定特定的治疗策略。
