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结肠癌切除术后的淋巴结获取量:错配修复缺失是一个因素吗?

Lymph node yield after colectomy for cancer: is absence of mismatch repair a factor?

作者信息

Samdani Tushar, Schultheis Molly, Stadler Zsofia, Shia Jinru, Fancher Tiffany, Misholy Justine, Weiser Martin R, Nash Garrett M

机构信息

1 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 2 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 3 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

出版信息

Dis Colon Rectum. 2015 Mar;58(3):288-93. doi: 10.1097/DCR.0000000000000262.

Abstract

BACKGROUND

Nodal staging is crucial in determining the use of adjuvant chemotherapy for colon cancer. The number of metastatic lymph nodes has been positively correlated with the number of lymph nodes examined. Current guidelines recommend that at minimum 12 to 14 lymph nodes be assessed. In some studies, mismatch repair deficiency has been associated with lymph node yield.

OBJECTIVE

The purpose of this work was to determine whether mismatch repair-deficient colorectal tumors are associated with increased lymph node yield.

DESIGN

We queried an institutional database to analyze colectomy specimens with immunohistochemistry for mismatch repair genes in patients treated for colorectal cancer between 1999 and 2012. Before 2006, immunohistochemistry was performed at the request of an oncologist or surgeon. After 2006, it was routinely performed for patients <50 years of age. We measured the association of clinical and pathologic features with lymph node quantity. Fourteen predictors and confounders were jointly analyzed in a multivariable linear regression model.

SETTINGS

The study was conducted at a single tertiary care institution.

PATIENTS

Tissue specimens from 256 patients were reviewed.

MAIN OUTCOME MEASURES

The correlation of tumor, patient, and operative variables to the yield of mesenteric lymph nodes was measured.

RESULTS

Of 256 colectomy specimens reviewed, 94 had mismatch repair deficiency. On univariate analysis, mismatch repair deficiency was associated with lower lymph node yield, older patient age, right-sided tumors, and poor differentiation. The linear regression model identified 5 variables with independent relationships to lymph node yield, including patient age, specimen length, lymph node ratio, perineural invasion, and tumor size. A positive correlation was observed with tumor size, specimen length, and perineural invasion. Tumor location had a more complex, nonlinear, quadratic relationship with lymph node yield; proximal tumors were associated with a higher yield than more distal lesions. Mismatch repair deficiency was not independently associated with lymph node yield.

LIMITATIONS

Mismatch repair immunohistochemistry based on patient age, family history, and pathologic features may reduce the generalizability of these results. Our sample size was too small to identify variables with small measures of effect. The retrospective nature of the study did not permit a true assessment of the extent of mesenteric resection.

CONCLUSIONS

Patient age, length of bowel resected, lymph node ratio, perineural invasion, tumor size, and tumor location were significant predictors of lymph node yield. However, when controlling for surgical and pathologic factors, mismatch repair protein expression did not predict lymph node yield.

摘要

背景

淋巴结分期对于确定结肠癌辅助化疗的使用至关重要。转移淋巴结的数量与检查的淋巴结数量呈正相关。当前指南建议至少评估12至14个淋巴结。在一些研究中,错配修复缺陷与淋巴结获取量有关。

目的

本研究的目的是确定错配修复缺陷的结直肠肿瘤是否与淋巴结获取量增加有关。

设计

我们查询了一个机构数据库,以分析1999年至2012年间接受结直肠癌治疗的患者的结肠切除术标本,采用免疫组织化学检测错配修复基因。2006年之前,免疫组织化学是应肿瘤学家或外科医生的要求进行的。2006年之后,对于年龄小于50岁的患者常规进行检测。我们测量了临床和病理特征与淋巴结数量之间的关联。在多变量线性回归模型中对14个预测因素和混杂因素进行了联合分析。

设置

本研究在一家三级医疗中心进行。

患者

对256例患者的组织标本进行了回顾性分析。

主要观察指标

测量肿瘤、患者和手术变量与肠系膜淋巴结获取量之间的相关性。

结果

在回顾的256例结肠切除术标本中,94例有错配修复缺陷。单因素分析显示,错配修复缺陷与较低的淋巴结获取量、患者年龄较大、右侧肿瘤以及低分化相关。线性回归模型确定了5个与淋巴结获取量有独立关系的变量,包括患者年龄、标本长度、淋巴结比率、神经周围侵犯和肿瘤大小。观察到肿瘤大小、标本长度和神经周围侵犯呈正相关。肿瘤位置与淋巴结获取量之间存在更复杂的非线性二次关系;近端肿瘤的淋巴结获取量高于更远端的病变。错配修复缺陷与淋巴结获取量无独立相关性。

局限性

基于患者年龄、家族史和病理特征的错配修复免疫组织化学可能会降低这些结果的普遍性。我们的样本量太小,无法识别效应量小的变量。本研究的回顾性性质不允许对肠系膜切除范围进行真正的评估。

结论

患者年龄、切除肠段长度、淋巴结比率、神经周围侵犯、肿瘤大小和肿瘤位置是淋巴结获取量的重要预测因素。然而,在控制手术和病理因素后,错配修复蛋白表达并不能预测淋巴结获取量。

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