术前、术中病理预测早期子宫内膜样腺癌高危因素的效果评价

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  【摘要】 目的 评价术前病理、术中肉眼判断肌层浸润深度及冰冻切片病理预测临床Ⅰ期子宫内膜腺癌高危因素[子宫内膜样腺癌病理分级为G3和(或)肌层浸润深度≥1/2者]的准确性和一致性。 方法 回顾性分析2000年1月~2010年6月在笔者所在医院妇科接受手术治疗的临床Ⅰ期子宫内膜腺癌102例患者的病理资料,以术后切除子宫病理诊断为“金标准”,评价预测高危因素的准确性和一致性。 结果 术前病理分级预测高危因素的敏感度为66.7%,特异度为93.8%,阳性预测值为73.7%,阴性预测值为91.6%, Kappa值为0.63。术中冷冻切片病理分级预测高危因素的敏感度为44.4%,特异度为91.4%,阳性预测值为61.5%,阴性预测值为84.1%,Kappa值为0.08。术中肉眼判断肌层浸润深度评价的敏感度为66.7%,特异度为86.4%,阳性预测值为56.0%,阴性预测值为90.9%,Kappa值为0.50。术中冰冻切片判断肌层浸润深度的敏感度为76.5%,特异度为89.8%,阳性预测值为68.4%,阴性预测值为93.0%,Kappa值为0.63。综合术前、术中病理预测高危因素的敏感度为79.4%,特异度为85.3%,阳性预测值为72.9%,阴性预测值为89.2%,Kappa值为0.63。 结论 术前病理分级与冷冻切片相比有较高准确性,与术后病理有较高的一致性。术中冷冻切片判断肌层浸润深度与术后病理有较高的一致性。综合术前、术中病理预测与术后病理有较高的一致性,判断不需行腹膜后淋巴结切除的可靠性较高,但对需行腹膜后淋巴结切除的可靠性稍低,术前分级和冰冻切片判断肌层浸润深度结合可能提高预测的准确性。
   【关键词】 子宫内膜癌; 诊断; 肿瘤分期; 肿瘤浸润
   Accuracy of preoperative and intraoperative pathological prediction in early endometrial adenocarcinoma SU Qing-hong,WANG Lan,GE Li-bin.The Seventh Affiliated Hospital of Guangxi Medical University,Wuzhou 543001,China
   【Abstract】 Objective To evaluate the accuracy and consistency of preoperative pathological mechanism,intraoperative assessment of myometrial invasion depth through naked eyes,and prediction of the high risk factor of endometrioid adenocarcinoma clinical stage I through frozen section pathological mechanism(the grade of pathological mechanism of endomatrioid adenocarcinoma is G3 and myometrial invasion depth ≥1/2). Methods To analyze the pathological mechanism materials of those 102 endometrioid adenocarcinoma stage I patients who received operation in our hospital retrospectively,evaluate the accuracy and consistency of the prediction of the high risk factor during 2000,1 to 2010,6,taken the pathologic diagnosis of hysterectomization after operation as “golden standard”. Results The sensitivity of prediction of high risk factor of the grade of preoperative pathological mechanism was 66.7%, the specificity was 93.8%,the positive predictive value was 73.7%,the negative predictive value was 91.6%,and Kappa value was 0.63.The sensitivity of prediction of high risk factor of the grade of intraoperative frozen section pathological mechanism was 44.4%,the specificity was 91.4%,the positive predictive value was 61.5%,the negative predictive value was 84.1%,and Kappa value was 0.08.The sensitivity of intraoperative assessment of myometrial invasion depth through naked eyes was 66.7%,the specificity was 86.4%,the positive predictive value was 56.0%,the negative predictive value was 90.9%,and Kappa value was 0.50.The sensitivity of intraoperative assessment of myometrial invasion depth of frozen section was 76.5%,the specificity was 89.8%,the positive predictive value was 68.4%,the negative predictive value was 93.0%,and Kappa value was 0.63.The sensitivity of prediction of high risk factor of preoperative,intraoperative pathological mechanism was 79.4%,the specificity was 85.3%,the positive predictive value was 72.9%,the negative predictive value was 89.2%,and Kappa value was 0.63. Conclusion The grade of preoperative pathological mechanism was more accurate than frozen section,and more consistency than pathological mechanism after operation,and intraoperative assessment of myometrial invasion depth of frozen section,prediction of high risk factor of preoperative,intraoperative pathological mechanism were more consistency.There was more reliability of assessment of unnecessary RPLND,but for the necessary RPLND the reliability is lower. The combination of the preoperation grade with the assessment of myometrial invasion depth of frozen section might promote the accuracy of prediction.
   【Key words】 Endometrial neoplasms; Diagnosis; Neoplasms taging; Neoplasms invasiveness
  doi:10.3969/j.issn.1674-4985.2012.05.001
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  子宫内膜癌是女性常见的恶性肿瘤,随着人类寿命的延长和肥胖人群的增多,其发病率有持续上升的趋势。子宫内膜癌的治疗趋于手术治疗为主的综合治疗。本研究收集临床Ⅰ期子宫内膜癌的临床病理资料,评价术前分段诊刮或宫腔镜活检病理分级(术前分级),术中肉眼判断肌层浸润深度及冰冻切片预测是否存在高危因素的准确性和与术后病理的一致性,为决定手术范围提供依据。
   1 资料与方法
  1.1 一般资料 回顾性分析2000年1月~2010年6月在笔者所在医院妇科手术治疗有完整临床病理资料的临床Ⅰ期子宫内膜腺癌患者108例,年龄36~72岁,所有的患者均行筋膜外全子宫切除术+双附件切除术,术前、术中预测有高危因素者行腹膜后淋巴切除。所有患者术前均未接受放疗、化疗或其他的抗肿瘤治疗,术后切除标本均送病理检查。
  1.2 方法
  1.2.1 组织病理分级:术前分段诊刮或宫腔镜活检的子宫内膜组织和术中切除子宫标本均送病理检查。依据FIGO推荐的组织学病理腺癌分级为:G1、G2、G3。
  1.2.2 诊疗过程:患者术前行分段诊刮或宫腔镜活检取得子宫内膜病理分级(术前病理分级)。基本手术方式是筋膜外全子宫切除术+双附件切除术,术中剖视子宫根据组织颜色和质地判断肌层浸润深度,部分切除子宫送冰冻切片获得病理分级及肌层浸润深度。根据术前病理分级、术中肉眼判断肌层浸润深度和冰冻切片病理判断有无高危因素而决定是否行腹膜后淋巴结切除。术后切除子宫标本均送病理检查,以术后病理为确诊标准。
  1.2.3 高危因素判定标准:子宫内膜样腺癌病理分级G1~G2和肌层浸润深度<1/2者为低危;子宫内膜样腺癌病理分级为G3和(或)肌层浸润深度≥1/2者为高危。
  1.3 术前、术中预测子宫内膜样腺癌高危因素的准确性评价指标 以术后切除子宫病理分级G3和(或)肌层浸润深度≥1/2者为“金标准”,术前、术中病理判断为高危,术后病理与以上两项中的一项相符为阳性,一项都不相符为假阳性;以术后切除子宫病理分级是G1~G2、肌层浸润深度<1/2者为“金标准”,术前、术中判断为低危,术后病理与以上两项相符为阴性,术后病理与以上两项之一不相符者为假阴性。
  1.4 统计学方法 使用SPSS 13.0软件进行统计分析,一致性评价采用Kappa检验。
   2 结果
  108例子宫内膜腺癌患者均行筋膜外全子宫切除术+双附件切除术,术中剖视子宫判断肌层浸润深度,76例切除子宫术中送冰冻切片,37例行腹膜后淋巴结切除。其中有3例术后病理没有发现肿瘤,而术前病理分级为G1,可能是子宫内膜微小癌灶经诊刮清除;3例术前病理为不典型增生、子宫内膜息肉,术后病理诊断为子宫内膜癌,这两种患者在计算时被剔除。
  2.1 术前病理分级、术中冰冻切片病理分级预测高危因素的准确性及一致性 102例患者中,术前病理分级为G1~G2者83 例,G3者19例,术后病理分级为G1~G2者81例,G3者21例(见表1),术前病理分级预测高危因素的敏感度为66.7%(14/21),特异度为93.8%(76/81),阳性预测值为73.7%,阴性预测值为91.6%, Kappa值为0.63。诊断符合率为88.24%(90/102)。
  术中冷冻切片病理分级为G1~G2者63例, G3者13例,术后病理分级为G1~G2者58例,G3者18例(见表2)。术中冷冻切片病理分级预测高危因素的敏感度为44.4%(8/18),特异度为91.4%(53/58),阳性预测值为61.5%,阴性预测值为84.1%,Kappa值为0.08。诊断符合率为80.3%(61/76)。
   2.2 术中肉眼判断、术中冰冻切片判断肌层浸润深度预测高危因素的准确性和一致性 术中肉眼判断肌层浸润深度<1/2者77例,≥1/2者25例,术后病理诊断肌层浸润深度<1/2者81例,≥1/2者21例,术中肉眼判断肌层浸润深度评价的敏感度为66.7%(14/21),特异度为86.4%(70/81),阳性预测值为56.0%,阴性预测值为90.9%,Kappa值为0.50。诊断符合率为82.4%(84/102)。见表3。
  
   术中冰冻切片判断肌层浸润深度<1/2者57例,≥1/2者19例,术后病理诊断肌层浸润深度<1/2者59例,≥1/2者17 例,术中冷冻切片判断肌层浸润深度的敏感度为76.5%(13/17),特异度为89.8%(53/59),阳性预测值为68.4%,阴性预测值为93.0%,Kappa值为0.64。诊断符合率为86.8%(66/76)。见表4。
  2.3 术前、术中病理预测子宫内膜样腺癌高危因素评价的准确性 根据术前病理分级和术中冰冻切片预测为低危者65例,高危者37例,术后切除子宫病理诊断为低危者68例,高危者34例,术前、术中病理预测高危因素的敏感度为79.4%(27/34),特异度为85.3%(58/68),阳性预测值为72.9%,阴性预测值为89.2%,Kappa值为0.63。诊断符合率为83.3%(85/102)。见表5。
  
   3 讨论
   子宫内膜癌是女性常见的恶性肿瘤,子宫内膜癌的治疗趋于手术治疗为主的综合治疗模式,对于临床Ⅰ期子宫内膜样腺癌是否要切除腹膜后淋巴结尚存在争议。Boronow等[1]报道低危者即Ⅰa~Ⅰb和G1、G2,淋巴结转移的风险可以忽略。临床随机研究显示,腹膜后淋巴结清扫有助于手术分期,但并不能提高患者的5年无病生存率或整体生存率[2,3]。目前许多医疗机构对判定有高危因素者行腹膜后淋巴结切除,而判定为低危因素者,如无肉眼可见的子宫外扩散病灶则不行腹膜后淋巴结切除。因此,术前、术中的病理分级和肌层浸润深度的准确判断成为准确选择手术范围的决定因素。
  通过分段诊刮、宫腔镜活检等方法取得术前病理分级。分段诊刮病理分级与术后病理分级存在不一致[4],约有18%~25%的术后病理分级上升[5,6]。术后病理分级上升,有可能导致治疗不足。冰冻切片也存在类似的情况[7]。本研究术前分级预测高危因素的敏感度为66.7%,特异度为93.8%,Kappa值为0.63。术中冰冻切片病理分级预测高危因素的敏感度为44.4%,特异度为91.4%,Kappa值为0.08,与Sanjuán等[8]报道相似。术前病理分级预测高危因素的准确性指标较高,与术后病理有较高的一致性(Kappa值为0.63)。判断肌层浸润深度的方法通常有CT、MRI、B超、术中肉眼判断、冰冻切片等。本研究的术中肉眼判断肌层浸润深度的敏感度为66.7%,特异度为86.4%,Kappa值为0.50,与Obrzut等[9]报道相似。术中冰冻切片判断肌层浸润深度的敏感度为76.5%,特异度为89.8%,阳性预测值为68.4%,阴性预测值为93.0%,Kappa值为0.64。冰冻切片预测高危因素的准确性指标较高,术中冰冻切片判断肌层浸润深度与术后病理有较高的一致性(Kappa值为0.64)。在临床实践中,手术者必须根据子宫内膜腺癌的病理分级和肌层浸润深度判断是否切除腹膜后淋巴结,因此需同时评价子宫内膜腺癌的病理分级和肌层浸润深度。本研究根据术前病理分级、术中肉眼判断肌层浸润深度、冰冻切片综合预测存在高危因素的敏感度为79.4%,特异度为85.3%,阳性预测值为72.9%,阴性预测值为89.2%, Kappa值为0.63,与Sanjuán等[8]报道相似。术前、术中病理结合与术后病理有较高的一致性(Kappa值为0.63)。判断不需行腹膜后淋巴结切除的可靠性较高(阴性预测值为89.2%),发生过度治疗的可能性较小;但对需行腹膜后淋巴结切除的可靠性稍低(阳性预测值为72.9%),部分病例可能发生治疗不足,手术医生应根据其他临床指标进行考虑。术前预测高危因素的准确性较冰冻切片判断肌层浸润深度预测高危因素的准确性高,两者相结合可能提高预测高危因素的准确性,从而减少治疗不足。
   参 考 文 献 
  [1] Boronow RC,Morrow CP,Creasman WT,et al.Surgical staging in endometrial cancer:clinical-pathologic findings of a prospective study[J].Obstet Gynecol,1984,63(6):825-832.
  [2] Benedetti Panici P,Basile S,Maneschi F,et al.Systematic pelvic lymphadenectomy vs.no lymphadenectomy in early-stage endometrial carcinoma:randomized clinical trial[J].J Natl Cancer Inst,2008,100(23):1707-1716.
  [3] Amos C,Blake P,Branson A,et al.Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial):a randomised study[J].Lancet,2009,373(9658):125-136.
  [4] Wang X,Huang Z,Di W,et al.Comparison of D&C and hysterectomy pathologic findings in endometrial cancer patients[J].Arch Gynecol Obstet,2005,272(2):136-141.
  [5] Cho H,Kim YT,Kim JH.Accuracy of preoperative tests in clinical stage I endometrial cancer:the importance of lymphadenectomy[J].Acta Obstet Gynecol Scand,2010,89(2):175-181.
  [6] Fotiou S,Trimble EL,Papakonstantinou K,et al.Complete pelvic lymphadenectomy in patients with clinical early,grade I and Ⅱ endometrioid corpus cancer[J].Anticancer Res,2009,29(7):2781-2785.
  [7] Case AS,Rocconi RP,Straughn JM Jr,et al.A prospective blinded evaluation of the accuracy of frozen section for the surgical management of endometrial cancer[J].Obstet Gynecol,2006,108(6):1375-1379.
  [8] Sanjuán A,Cobo T,Pahisa J,et al.Preoperative and intraoperative assessment of myometrial invasion and histologic grade in endometrial cancer:role of magnetic resonance imaging and frozen section[J].Int J Gynecol Cancer,2006,16(1):385-390.
  [9] Obrzut B,Obrzut M,Skret-Magier?o J,et al.Value of the intraoperative assessment of the depth of myometrial invasion in endometrial carcinoma[J].Ginekol Pol,2008,79(6):404-409. 
   (收稿日期:2011-11-30)
   (本文编辑:王宇)
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基金项目:虹膜固定型人工晶状体和后房型人工晶体双襻缝线固定术治疗无后囊无晶状体眼临床对比观察(编号:2007105150099)  作者单位:523900 广东省东莞市太平人民医院  通讯作者:梁永强  【摘要】 目的 评价虹膜固定型人工晶状体和后房型人工晶体双襻缝线固定术治疗无晶状体眼的疗效。方法 无后囊膜无晶状体眼105例(110眼),55眼行虹膜固定型人工晶体植入术,55眼行后房型人工晶
目的:通过检测胃泌素及丙谷胺干预下胃癌MKN45细胞DNMT-1基因表达与E-Cadherin和MMP-2基因甲基化变化的相关性。方法:胃癌细胞株分别在胃泌素和丙谷胺干预下分为空白组、胃泌素
目的探讨内皮抑素表达与肾细胞癌微血管密度及预后的关系。方法采用免疫组化的方法检测45例原发性肾细胞癌组织及35例癌旁正常肾组织中的Endostatin及CD34,并观察Endostatln的