早期肠型胃腺癌中肿瘤出芽的分级及其在淋巴结转移风险评估中的意义

Grading of tumor budding in intestinal-type early gastric adenocarcinoma and its role in assessing the risk of lymph node metastasis

目的探讨早期肠型胃腺癌的肿瘤出芽(tumor budding)在预测淋巴结转移时的价值,确定预测效果最佳肿瘤出芽个数的划分截值。方法收集南京医科大学附属无锡人民医院2008-2018年早期肠型胃腺癌手术根治标本共202例。根据国际肿瘤出芽共识会议(ITBCC)确立的标准(肿瘤出芽定义、观测面积和计数方法),计数每例标本的肿瘤出芽个数。受试者工作特征(ROC)曲线分析肿瘤出芽对淋巴结转移的预测效能并确定最佳划分截值。Logsitic多因素回归评估较高的肿瘤出芽数量是否为淋巴结转移的独立危险因素。分析符合内镜切除标准且发生淋巴结转移的病例中,是否具有较高肿瘤出芽的数量。结果63.4%(128/202)的早期肠型胃腺癌存在肿瘤出芽。ROC曲线分析显示,以4个肿瘤出芽为截值时预测淋巴结转移的效果最佳(曲线下面积0.767,灵敏度0.657,特异度0.780)。据此将202例病例分为2组:≥4个肿瘤出芽为高出芽组(60例);<4个肿瘤出芽为低出芽组(142例);前者淋巴结转移风险高于后者(41.7%比9.1%,P<0.01)。肿瘤出芽数量与肿瘤侵犯深度、淋巴管侵犯密切相关(均P<0.01)。多因素回归分析显示,≥4个肿瘤出芽是发生淋巴结转移的独立危险因素(HR 8.760,95%CI 2.648~28.987;P<0.01)。同时,以4个肿瘤出芽为截值预测淋巴结转移的效果优于ITBCC推荐的划分截值。此外,有3例符合早期胃癌内镜切除标准(扩展适应证)的病例发生淋巴结转移,而其中2例患者的肿瘤出芽数量均≥4个。结论≥4个肿瘤出芽是预测早期肠型胃腺癌淋巴结转移的有用指标,可作为内镜治疗标准的有益补充以识别淋巴结转移高风险的患者。

Objective To investigate the role of tumor budding(TB)in predicting lymph node metastasis of intestinal-type early gastric adenocarcinoma,and to determine the optimal cutoff value of TB number.Methods A total of 202 patients with intestinal-type early gastric adenocarcinoma,who underwent surgical operation at the Affiliated Wuxi People′s Hospital of Nanjing Medical University,Jiangsu,China from 2008 to 2018 were included.According to the International Tumor Budding Consensus Conference(ITBCC)criteria,the number of TB for each case was assessed.The receiver operating characteristic(ROC)curve was employed to determine the optimal cutoff value of TB number for predicting lymph node metastasis,and multivariate logistic regression was used to analyze whether a high TB number was an independent risk factor for lymph node metastasis.In addition,in the patients,who met the indications for endoscopic resection and developed lymph node metastasis,the association of a high number of TB with lymph node metastasis was examined.Results TBs were observed in 63.4%(128/202)of intestinal-type early gastric adenocarcinomas.Using ROC curve,4 TBs was found as the optimal cutoff value to predict lymph node metastasis(area under the curve 0.767;sensitivity 0.657;specificity 0.780).Therefore,the 202 cases were divided into two groups:the high-budding(≥4 TBs)group(n=60)and the low-budding(<4 TBs)group(n=142).The high-budding group exhibited a higher rate of lymph node metastasis than that of the low-budding group(41.7%vs 9.1%,P<0.01),and≥4 TBs was associated with deeper invasion and lymph vessel invasion(P<0.01).The multivariate regression model showed that≥4 TBs was an independent risk factor for lymph node metastasis(Hazard ratio=8.760,95%CI 2.648-28.987;P<0.01).Meanwhile,4 TBs as the cutoff value could better predict lymph node metastasis than the cutoff value advised by the ITBCC.In addition,3 cases were found to have developed lymph node metastasis even that they met the expanded indications for endoscopic resection,and 2 of these 3 cases exhibited a higher TB number(≥4 TBs).Conclusions More than 4 TBs are a useful indicator for predicting lymph node metastasis in intestinal-type early gastric adenocarcinoma.It may be used to as an endoscopic resection criterion for patients with a high risk of lymph node metastasis.