【作者】 刘乃富；

【导师】 薛凤霞；

【作者基本信息】 天津医科大学 ， 妇产科学， 2010， 博士

【摘要】 目的：探讨前哨淋巴结(sentinel lymph node, SLN)在早期子宫内膜癌中的诊疗意义,99mTc标记前哨淋巴结活检术(sentinel lymph node biopsy, SLNB)的放射安全性及替代腹膜后淋巴清扫术的可行性。研究SLNB术前淋巴显像和SLN在术中病理诊断作用。建立合适的SLN微转移病理诊断模式。材料与方法：2007年11月起使用99mTc标记的硫胶体对在山东省肿瘤医院妇瘤科接受全面分期手术的59例子宫内膜癌患者先行SLNB,之后行盆腹腔淋巴结清扫术。使用热释光剂量计(TLD)检测57例患者SLNB过程中宫腔、胸腺、盆腔性腺及医务人员手食指、胸腺、盆腔性腺、眼晶体的放射剂量。分析术前淋巴显像与术中γ探测仪检测SLN的结果。对SLN进行术中印片细胞学、快速冰冻病理检查及术中加强聚合体一步染色法免疫组织化学染色(EPOS)。应用连续切片(SS)病理分析联合免疫组化(IHC),对45例患者常规病理阴性的111个SLN以100μm间距SS,每个切片均行H-E染色病理分析和IHC检测。比较不同检测方法和不同间距SS对转移灶检出率的影响。结果：59例患者SLN检出成功率为96.6%(57／59),准确率为96.1%,假阴性率为8.3%。97.7%的SLN位于盆腔,特别是闭孔和髂内淋巴结。SLNB的成功率和假阴性率与患者年龄、肿瘤大小、位置、病理类型、肌层侵犯深度、CA125水平等因素无关。热释光剂量计显示患者宫腔部位的吸收剂量显著高于胸腺及盆腔性腺。手术人员主要部位的核素吸收剂量无统计学差异,远低于卫生部确定的放射卫生防护基本标准。术者每年行1000台SLNB手术是安全的。淋巴显像成功确定52例患者的SLN,成功率88.1%。确定SLN的淋巴显像失败率与肿瘤的部位、病理类型、肌层浸润深度和注射同位素到显像的时间无显著相关性。术中确定SLN的成功率与术前淋巴显像成功组和失败组之间存在显著性差异。术前淋巴显像是否成功确定SLN与SLNB的假阴性率无显著相关性。128个SLN的印片细胞学诊断的灵敏度为52.9%、特异度86.5%、假阴性率47.1%、假阳性率13.5%、准确率82.0%。术中冰冻快速病理诊断的灵敏度为88.2%、特异度100%、假阴性率11.8%、假阳性率0、准确率98.4%。EPOS快速免疫组化角蛋白阳性反应,诊断的灵敏度100%,特异度100%,假阴性率0,假阳性率0,准确率100%。术中冰冻病理联合EPOS快速诊断的灵敏度为100%、特异度100%、假阴性率0、假阳性率0、准确率100%。术中冰冻病理联合印片细胞学诊断的灵敏度为94.1%、特异度100%、假阴性率5.9%、假阳性率0、准确率99.2%。45例患者SLN通过SS病理分析和IHC阳性检出率分别提高11.1%和15.6%。联合IHC新增SLN阳性检出8例,对转移灶的检出,联合法与H-E染色病理检测相比无显著性差异。对MMs的检出,H-E染色发现3例,IHC发现4例,联合法发现4例,H-E染色法与联合法有显著性差异。针对ITCs,H-E染色发现1例,IHC发现1例,联合法发现2例,H-E染色法与联合法有显著性差异。1175个层面中,联合IHC比SS病理新增阳性层面35层。H-E染色法与联合法对于阳性层面的检出有显著性差异。多层切片H-E染色分析间距300μm MMs的检出有显著优势。结论：①SLN可以准确预测早期子宫内膜癌腹膜后淋巴结的转移状况。②SLN主要位于髂内和闭孔组淋巴结。③SLN检出成功率和假阴性率与患者的年龄、肿瘤大小、位置、病理类型、肌层侵犯深度、CA125水平等因素无关。.④临床早期子宫内膜癌SLNB准确性达到了替代盆腹腔淋巴清扫术的要求。⑤核素法SLNB对患者和医务人员是安全的,无需防护。术者每年完成1000台SLNB手术是安全的。⑥术前淋巴显像可预测术中SLN检出成功率,有助于确定盆腔以外的SLN,但术前淋巴显像并非SLNB所必需。⑦通过联合术中快速病理检查、印片细胞学及EPOS快速免疫组化角蛋白检测可以较准确的判断SLN的病理情况；⑧SS HE病理分析较常规HE病理分析对SLN微转移(MMs)的检出有显著优势；联合IHC比SSHE病理分析显著提高MMs、孤立肿瘤细胞(ITCs)检出率；300μm是SS HE病理检测的最佳间距。更多还原

【Abstract】 Objective The purpose of this study was to research treatment significance of SLN in early-stage endometrial cancer, radiologic safety of SLNB marked with 99mTC and feasibility of SLNB as an alternative to systematic lymphadenectomy. simultineously, the value of preoperative lymphoscintigraphy in SLNB and intraoperative diagnosis of SLN in endometrial cancer. To set up proper pathological detection methods of micrometastasis in SLN. Methods 59 patients from September 2007, who underwent comprehensive staging surgery, were treated with SLNB followed by systematic lymphadenectomy using 99mTc. TLD was used to detect radiation dose received by patients and medical stuff in 57 patients. Analyzed the results of SLNs in preoperative lymphoscintigraphy and intraoperative detection of gamma detector. Pathological diagnosis was used for the intraoperative diagnosis of SLNs. SS pathological analysis combined with IHC,111 SLNs of 45 patients were identified negative by HE using SS at 100μm intervals, H-E and IHC staining were performed for each slice. Compare the effect on metastasis detection rate between different methods and intervals.Results SLNs were successfully identified in 57 of 59 (96.6%) patients, the accuracy rate was 96.1%, with 8.3% false negative rate.97.7% of SLNs were located at pelvic. No relationships were found of the success rate and false negative rate with Clinicopathological factors. The radiation dose received at the uterine cavity was significantly higher than that at the thoracic gland and cavitas pelvis gonad of the patients. The radiation dose is safe to patients and medical stuff, and annually surgeons perform 1000 SLNBs safely also.SLNs from 52 patients were determined successfully by lymphoscintigraphy, success rate was 88.1%. The failure rate of SLN in lymphoscintigraphy was not associated with histopathologic type, tumor location and myometrial invasion, and time interval from injection of radiocolliod to surgery. There was a significant difference between the success rate of SLN in operation and the successful and failure group of pre-operation lymphoscintigraphy. Whether lymphoscintigraphy image succeeds or not identified, that there was no significant difference in the false negative rate.The diagnoses of TIC of 128 SLNs were as follows:sensitivity 52.9%, specificity 86.5%, false negative rate 47.1%, false positive rate 13.5%, and accuracy 82.0%, respectively. The intraoperative pathological diagnoses with frozen section、EPOS and combined diagnoses of intraoperative frozen and TIC were as fellows:sensitivity 88.2%.100%、94.1%, specificity 100%、100%、100%, false negative rate 11.8%、0%、5.9%, false positive rate 0、0、0, and accuracy 98.4%、100%、99.2%, respectively. In 45 SLN negative cases, using SS and combined with IHC, positive detection rate increased 11.1% and 15.6%, respectively. Combined with IHC,8 cases of positive SLN were added. For the detection of MMs, 3 cases by H-E staining,4 cases by IHC and 4 cases by SS combined with IHC. There was a great difference between the method of H-E staining and SS combined with IHC. For ITCs,1 case by H-E staining,1 case by IHC and 2 cases by SS combined with IHC. There was a great difference between the method of H-E staining and SS combined with IHC. In all 1175 slides,35 slides were added by SS combined with IHC than that of SS pathology. Significance could be drawn between the method of H-E stain and SS combined with IHC for the detection of positive slides. Rate of detection of MMs in 300μm had a significant advantage. Conclusion①SLN could accurately predict retroperitoneal lymph node status in early-stage endometrial cancer.②Most of SLNs were located at pelvic, espescially internal iliac and obturator node.③No relations were found between the success rate, false negative rate and age, tumor size, tumor location, histopathological type, myometrial invasion, level of CA125.④The accuracy rate was high enough for SLNB as an alternative to systematic retroperitoneal lymphadenectomy in endometrial cancer.⑤The SLNB in endometrial cancer was radiologically safe both for patients and medical stuff, It was safe for surgeons to perform 1000 SLNBs annually.⑥Preoperative lymphoscintigraphy was unnecessary for operation.⑦The combined intraoprative diagnosis of SLNs with frozen section and EPOS immunohistochemistry or TIC had very high accuracy and very low false negative rate.⑧SS H-E combined with IHC could further significantly improve the detection of SLN MMs compared to SS H-E alone.300-μm might be the optimal interval for SS.更多还原