前哨淋巴结检测技术在子宫内膜癌中的应用

子宫内膜癌是女性常见的恶性肿瘤,手术是子宫内膜癌的主要治疗手段,除了不能耐受手术或晚期无法进行手术的患者外,其他患者均应进行全面的分期手术。随着精准化治疗时代的到来,前哨淋巴结(SLN)检测技术在子宫内膜癌中的应用日趋成熟,但关于SLN显像染料和注射部位的选择及病理超分期技术的临床意义仍未达成共识。吲哚菁绿(ICG)相比于其他染料能提高双侧盆腔SLN的检出率,且不良反应发生率低。宫颈注射具有操作方便和盆腔SLN检出率高的优势;病理超分期技术能提高微转移病灶的检出率,但临床意义尚未明确。如何更好地提高SLN的检出率、降低SLN的假阴性率、避免不必要的全面淋巴结清扫术并指导临床预后成为当前研究的重点。本文就SLN技术在子宫内膜癌中的应用情况进行阐述。     

子宫内膜癌前哨淋巴结应用的研究进展与展望

前哨淋巴结（sentinel lymph node，SLN）检测为子宫内膜癌患者的精准淋巴结切除提供了选择，极具应用前景，但仍有部分问题和争议亟待解决，如SLN检测在高危患者中的标准临床应用规范、SLN最佳算法、评估SLN的最佳方式、低体积转移的临床意义，均值得探究。目前子宫颈注射吲哚菁绿为最常用的示踪方法，病理学超分期可提高对低体积转移的检出率，但病理学超分期操作流程、应用指征及低体积转移的临床管理需进一步规范。此外，高危型子宫内膜癌并非SLN检测的绝对禁忌证，但此类患者行SLN检测的标准临床应用规范有待进一步研究。现就近年来子宫内膜癌SLN检测研究现状及进展进行综述。     

前哨淋巴结在88例早期子宫内膜癌术中的应用

摘 要：［目的］ 分析前哨淋巴结（sentinel lymph node,SLN）在早期子宫内膜癌术中的应用价值。［方法］ 将88例行手术治疗的早期子宫内膜癌患者纳入研究,行亚甲蓝注射液前哨淋巴结显影探查;记录SLN检出情况和盆腔淋巴结转移情况。［结果］ ①前哨淋巴结检出率（SLN阳性率）为94.32%。②肿瘤直径≤2cm 的患者SNL检出率为100.00%,肿瘤直径＞2cm 的患者SLN检出率为87.00%。SNL检出率在不同注射位置及不同年龄段中无明显差异。③SLN与盆腹腔淋巴结分布：45.76%SLN分布在髂外,其次为闭孔（23.99%）;37.99%的盆腹腔淋巴结分布在髂外,29.06%分布在闭孔。④亚甲蓝注射液示踪SNL诊断盆腔淋巴结转移特异性、敏感度分别为95.58%和100.00%。 ［结论］ 示踪前哨淋巴结用于早期子宫内膜癌术中能清晰显影淋巴管,能辅助判断盆腹腔淋巴结是否转移,对淋巴结精准清扫、治疗及预后有指导意义。     

纳米碳在子宫内膜癌前哨淋巴结检测中的应用

目的:探讨纳米碳在子宫内膜癌前哨淋巴结检测中的可行性及应用价值。方法:选择25例经手术治疗的子宫内膜癌患者,术中于子宫前壁、后壁、宫底两侧共4点处注射纳米碳混悬液,识别黑染的淋巴结,并记录前哨淋巴结相关信息,淋巴结分开单独送病理检查行HE染色。结果:25例子宫内膜癌患者均出现子宫浆膜面黑染,前哨淋巴结检出率为84%（21/25）,共计114枚,其中盆腔双侧检出率为81%,盆腔一侧检出率为19%。3例患者发生淋巴结转移,均为SLN转移。结论:纳米碳作子宫内膜癌前哨淋巴结的示踪剂具有可行性,对于子宫内膜癌淋巴结转移判断有一定的临床应用价值。     

不同部位注射纳米炭在腹腔镜子宫内膜癌前哨淋巴结示踪情况的对比研究北大核心

目的:探讨不同部位注射纳米炭在腹腔镜子宫内膜癌手术前哨淋巴结(sentinel lymph node,SLN)检测中的应用价值,探索最优化的SLN示踪方案。方法:选取2018年03月至2021年06月接受腹腔镜手术的子宫内膜癌患者共76例,随机分为宫颈注射组(39例)及宫底注射组(37例),以纳米炭作为示踪剂多点注射于宫颈或宫底部,在腹腔镜下观察显影的第一站淋巴结并切除后送病理检查,再采取标准的子宫、双附件切除及系统的盆腔淋巴结切除术和/或腹主动脉旁淋巴结切除术。比较两组患者的SLN检出率、检出部位、敏感度、假阴性率、阴性预测值。结果:两组患者总体SLN检出率为81.5%,检出位置:最常见于髂外区21例(33.8%),然后依次为闭孔区16例(25.8%)、髂内区14例(22.6%)、髂总区7例(11.3%)、腹主动脉旁区域3(3.9%)、骶前1例(1.6%)。宫颈注射组在盆腔SLN检出方面更有优势,宫底注射组在腹主动脉旁区域SLN检出方面更有优势。7例(9.2%)发生盆腔淋巴结转移,其中4例在宫颈注射组,敏感度为75%(3/4),假阴性率为25%(1/4),阴性预测值97.1%(34/35)。3例在宫底注射组,敏感度为66.7%(2/3),假阴性率为33.3%(1/3),阴性预测值为96.9%(32/33)。结论:纳米炭应用于腹腔镜子宫内膜癌SLN活检安全高效、操作简便,宫颈注射组更方便,有更好的盆腔SLN检出率,但宫底注射组有更好的腹主动脉旁SLN检出率,值得进一步应用研究。     

cN0喉癌前哨淋巴结的检测及意义

目的 应用核素法、染料法以及二者联合法检测cN0喉癌患者前哨淋巴结(SLN),并评价SLN对颈部淋巴结转移状况的预测价值.方法 41例cN0喉癌患者采用核素法、染料法和联合法示踪SLN.核素法为手术前于喉镜引导下在肿瘤周围注射99TCm-硫胶体(SC)进行SLN显像,手术中用γ探针探测放射性"热点";染料法为手术中注射亚甲蓝,示踪蓝染的SIN;联合法为将核素法和染料法联合应用的方法.结果 核素法、染料法和联合法对SLN的检出率分别为87.8%、70.7%和92.7%(P<0.01);核素法与联合法、染料法与联合法检出SIN数目的 差异有统计学意义(P<0.05,P<0.01),核素法与染料法检出SLN数目的 差异无统计学意义(P>0.05).病理结果示,有9例患者淋巴结转移,占22.0%.联合法检测SLN的灵敏度、准确度和阴性预测值分别为88.9%、97.4%和96.7%.结论 联合应用核素法和染料法可提高SEN检出的准确性,SLN的病理结果可以准确预测cN0喉癌患者颈部淋巴结的病理状态.     

cN0喉癌前哨淋巴结的检测及意义

目的 应用核素法、染料法以及二者联合法检测cN0喉癌患者前哨淋巴结(SLN),并评价SLN对颈部淋巴结转移状况的预测价值.方法 41例cN0喉癌患者采用核素法、染料法和联合法示踪SLN.核素法为手术前于喉镜引导下在肿瘤周围注射99TCm-硫胶体(SC)进行SLN显像,手术中用γ探针探测放射性"热点";染料法为手术中注射亚甲蓝,示踪蓝染的SIN;联合法为将核素法和染料法联合应用的方法.结果 核素法、染料法和联合法对SLN的检出率分别为87.8%、70.7%和92.7%(P<0.01);核素法与联合法、染料法与联合法检出SIN数目的 差异有统计学意义(P<0.05,P<0.01),核素法与染料法检出SLN数目的 差异无统计学意义(P>0.05).病理结果示,有9例患者淋巴结转移,占22.0%.联合法检测SLN的灵敏度、准确度和阴性预测值分别为88.9%、97.4%和96.7%.结论 联合应用核素法和染料法可提高SEN检出的准确性,SLN的病理结果可以准确预测cN0喉癌患者颈部淋巴结的病理状态.     

cN0喉癌前哨淋巴结的检测及意义

目的 应用核素法、染料法以及二者联合法检测cN0喉癌患者前哨淋巴结(SLN),并评价SLN对颈部淋巴结转移状况的预测价值.方法 41例cN0喉癌患者采用核素法、染料法和联合法示踪SLN.核素法为手术前于喉镜引导下在肿瘤周围注射99TCm-硫胶体(SC)进行SLN显像,手术中用γ探针探测放射性"热点";染料法为手术中注射亚甲蓝,示踪蓝染的SIN;联合法为将核素法和染料法联合应用的方法.结果 核素法、染料法和联合法对SLN的检出率分别为87.8%、70.7%和92.7%(P<0.01);核素法与联合法、染料法与联合法检出SIN数目的 差异有统计学意义(P<0.05,P<0.01),核素法与染料法检出SLN数目的 差异无统计学意义(P>0.05).病理结果示,有9例患者淋巴结转移,占22.0%.联合法检测SLN的灵敏度、准确度和阴性预测值分别为88.9%、97.4%和96.7%.结论 联合应用核素法和染料法可提高SEN检出的准确性,SLN的病理结果可以准确预测cN0喉癌患者颈部淋巴结的病理状态.     

cN0喉癌前哨淋巴结的检测及意义

目的 应用核素法、染料法以及二者联合法检测cN0喉癌患者前哨淋巴结(SLN),并评价SLN对颈部淋巴结转移状况的预测价值.方法 41例cN0喉癌患者采用核素法、染料法和联合法示踪SLN.核素法为手术前于喉镜引导下在肿瘤周围注射99TCm-硫胶体(SC)进行SLN显像,手术中用γ探针探测放射性"热点";染料法为手术中注射亚甲蓝,示踪蓝染的SIN;联合法为将核素法和染料法联合应用的方法.结果 核素法、染料法和联合法对SLN的检出率分别为87.8%、70.7%和92.7%(P<0.01);核素法与联合法、染料法与联合法检出SIN数目的 差异有统计学意义(P<0.05,P<0.01),核素法与染料法检出SLN数目的 差异无统计学意义(P>0.05).病理结果示,有9例患者淋巴结转移,占22.0%.联合法检测SLN的灵敏度、准确度和阴性预测值分别为88.9%、97.4%和96.7%.结论 联合应用核素法和染料法可提高SEN检出的准确性,SLN的病理结果可以准确预测cN0喉癌患者颈部淋巴结的病理状态.     

cN0喉癌前哨淋巴结的检测及意义

目的 应用核素法、染料法以及二者联合法检测cN0喉癌患者前哨淋巴结(SLN),并评价SLN对颈部淋巴结转移状况的预测价值.方法 41例cN0喉癌患者采用核素法、染料法和联合法示踪SLN.核素法为手术前于喉镜引导下在肿瘤周围注射99TCm-硫胶体(SC)进行SLN显像,手术中用γ探针探测放射性"热点";染料法为手术中注射亚甲蓝,示踪蓝染的SIN;联合法为将核素法和染料法联合应用的方法.结果 核素法、染料法和联合法对SLN的检出率分别为87.8%、70.7%和92.7%(P<0.01);核素法与联合法、染料法与联合法检出SIN数目的 差异有统计学意义(P<0.05,P<0.01),核素法与染料法检出SLN数目的 差异无统计学意义(P>0.05).病理结果示,有9例患者淋巴结转移,占22.0%.联合法检测SLN的灵敏度、准确度和阴性预测值分别为88.9%、97.4%和96.7%.结论 联合应用核素法和染料法可提高SEN检出的准确性,SLN的病理结果可以准确预测cN0喉癌患者颈部淋巴结的病理状态.     

Current position of the sentinel lymph node procedure in endometrial cancer

Lymph node status is a major prognostic element in endometrial cancer and affects the choice of adjuvant therapy. The sentinel lymph node (SLN) procedure is proposed as an alternative to lymphadenectomy. This review aims to assess its feasibility. To this end, 19 studies have been analysed. It appears that double detection (colorimetric and isotopic) is better than single detection, independent of injection site. Hysteroscopic injection is technically more difficult, yet can be done near the tumoral lesion. The cervical site does not accurately reflect the lymphatic drainage of the uterine body but is easier to access. SLN detection rate is notably identical between these two injections sites. Lomboaortic detection rate is lower for cervical injections than for endometrial ones. The myometrial site is also difficult to access (intraoperatively), due to same limitations as the hysteroscopic route, and can be deceiving (insufficient detection rate and high false-negative rate). The SLN allows for ultrastadification (micrometastases and isolated tumoral cells) with the development of new pathological techniques (serial sections and immunohistochemistry). Data on SLN in endometrial cancer is very heterogeneous in terms of methodology and populations studied. Despite being well-known, the SLN procedure in endometrial cancer remains in its feasibility stage. Its place in therapeutic strategies needs to be further explored and its potential benefit remains to be confirmed.     

The added value of SLN mapping with indocyanine green in low- and intermediate-risk endometrial cancer management: a systematic review and meta-analysis

ObjectiveThe aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG).MethodsA systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion.ResultsFourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%–97.9%) and 76.5% (95% CI=68.1%–84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%–15.2%) in patients with grade 1–2 endometrial cancer and 11.8% (95% CI=8.1%–16.1%) in patients with grade 1–3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%–100%) in studies that included grade 1–2 endometrial cancer and 99.2% (95% CI=97.9%–99.9%) in studies that also included grade 3.ConclusionSLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer.     

Sentinel lymph node biopsy in cervical and endometrial cancers: a feasibility study

The sentinel lymph node (SLN) biopsy has been proposed for the cancers of the uterus in order to optimize the diagnosis of lymphatic metastases and micrometastases in early stage tumors. Patients with early invasive cervical (n = 8) or endometrial (n = 15) cancers were enrolled. A lymphoscintigraphy was carried out before the intervention. Intraoperative SLN identification was performed with blue dye combined to a handheld gamma probe detection. Non-sentinel pelvic nodes were separately cleared out. SLNs were examined with frozen sections, permanent sections with hematoxylin-eosin staining and further serial sections with immunohistochemistry if negative. Six cervical cancer patients and 13 endometrial cancer patients had a positive lymphoscintigraphy, showing in 5 patients extra-iliac SLN(s). The intraoperative detection was successful in 6 cervical cancer patients and 14 endometrial cancer patients. The higher detection rate was obtained with the isotopic method. Most of the SLNs were ilio-obturator. Four endometrial cancer patients had a lymphatic spread, only involving the SLN in each case. No false negative SLN has been noted. SLN biopsy appears feasible in cervical and endometrial cancers. This procedure could improve the lymphatic evaluation of these cancers.     

Preliminary study of sentinel node identification with 99mTc colloid and blue dye in patients with endometrial cancer

AIMS AND BACKGROUND: Intraoperative lymphatic mapping and sentinel node (SLN) biopsy have generated a tremendous amount of interest and are already established as part of the standard practice in the surgical management of breast cancer and melanoma. To reduce extensive radical procedures and decrease the morbidity in the treatment of gynecologic malignancies, much effort is being made to use less aggressive interventions. The purpose of our study was to determine the feasibility of SLN mapping in a group of patients with endometrial cancer at early stages. METHOD AND STUDY DESIGN: Between September 2000 and May 2001 11 patients with endometrial cancer FIGO stage Ib (n = 10) and IIa (n = 1) underwent laparoscopic SNL detection during laparoscopy-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and bilateral systematic pelvic lymphadenectomy. Radioactive isotope injection was performed 24 hours before surgery and blue dye injection was performed just before surgery in the cervix at 3,6, 9 and 12 hours. A 350 mm laparoscopic gamma scintyprobe MR 100 type 11, 99mTc settled (Pol Hi Tech), was used intraoperatively for SLN detection. RESULTS: Seventeen (17) SLNs were detected with lymphoscintigraphy (six bilateral and five unilateral). At laparoscopic surgery we found the same locations belonging at internal iliac lymph nodes (the so-called Lebeuf-Godard area, lateral to the inferior vesical artery, ventral to the origin of the uterine artery and medial or caudal to the external iliac vein). Fourteen (14) SLNs were negative on histological analysis and three were positive for micrometastases (mean SLN sections = 60). All other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with the gamma scintyprobe were observed at laparoscopy after patent blue dye injection. CONCLUSIONS: Our preliminary data suggest that combined 99mTc-labeled colloid and vital blue-dye techniques are feasible for SLA detection in endometrial cancer; they represent a very promising tool to transform the management of early-stage endometrial cancer. The clinical validity of this combined technique should be evaluated prospectively.     

Sentinel lymph node micrometastasis in human breast cancer: an update

Introduction

The advent of sentinel lymph node biopsy (SLNB) and advances in histopathological and molecular analysis techniques have been associated with an increase in micrometastasis (MM) detection rate. However, the clinical significance of sentinel lymph node micrometastasis (SLN MM) continues to be a subject of much debate. In this article we review the literature concerning SLN MM, with particular emphasis on the prognostic significance of SLN MM. The controversies regarding histopathological assessment, clinical relevance and management implications are also discussed.

Methods

Literature review facilitated by Medline and PubMed databases. Cross referencing of the obtained articles was used to identify other relevant studies.

Results

Published studies have reported divergent and rather conflicting results regarding the clinical significance and implications of axillary lymph node (ALN) MM in general and SLN MM in particular. Some earlier studies demonstrated no associations, however most recent studies have found SLN MM to be an indicator of poorer prognosis and to be associated with non-SLN involvement.The use of adjuvant chemotherapy and/or hormonal manipulation therapy is associated with an improved survival in patients with SLN MM. Complete ALND may be safely omitted provided that adjuvant systemic therapy recommendations are equal to patients with node-positive disease. However, optimal management of SLN MM is yet to conclude.Furthermore, the identification of MM remains largely dependant on the analytical technique employed and the use of immunohistochemistry (IHC) increases the detection rate of SLN MM. Discrepancies in the histopathological interpretation of TNM classification of SLN tumour burden do exist. Published studies were non-randomized and have significant limitations including a small sample size, limited follow-up period, and lack of standardization and reproducibility of pathological examination of the SLN.

Conclusion

Patients with SLN MM have a poorer prognosis than those who are SLN negative. Therapeutic recommendations regarding patients with SLN MM should be taken in the context of multidisciplinary team setting and in selected cases of SLN MM, complete ALND may be safely omitted. A better reproducibility of pathological interpretation of the TNM classification is required so that future therapeutic guidelines can be applied without confusion.     

Sentinel Lymph Node in Endometrial Cancer: A Review

Lymph node status is a major prognostic factor in endometrial cancer (EC). Sentinel lymph node (SLN) biopsy has been reported in EC for more than 15 years but has not yet been incorporated as a standard-of-care procedure in EC. Complex uterine drainage, the various modalities of tracer injection, and the lack of large prospective series may explain this situation. In this review, we report an SLN detection rate of 81.7 %, a 10.9 % rate of metastatic SLN involvement, and a false-negative rate of 12.3 % in the main clinical trials. Thirty-five percent of SLN metastases were low-volume disease (micrometastases or isolated tumor cells). These data raise the question of the clinical significance of low-volume disease in EC. SLN biopsy could allow upstaging in supposedly low- or intermediate-risk patients in whom adjuvant therapy could be omitted. Further studies are required to precise the interest on the survival of this procedure in this subset of patients.     

99mTc-硫胶体术前淋巴显像在乳腺癌前哨淋巴结活检中的应用*

目的:探讨用99mTc- 硫胶体（99mTc-Sulfur colloid ,SC）术前淋巴显像在乳腺癌前哨淋巴结活检（sentinel lymph node biopsy ,SLNB）中的临床应用。方法:选择2009年7 月到2010年1 月本院收治的70例乳腺癌患者,于乳腺肿块周围3 点、6 点和12点位置各注射99mTc-Sc37MBq 后15min、30min、1h、2h 行前哨淋巴结（sentinel lymph node ,SLN ）显像,术中用γ 探针探测“热点”淋巴结分析术前淋巴显像与术中探测检测乳腺癌SLNB的结果。结果:术前99mTc-Sc 淋巴显像成功确定60例患者（85.71%）的前哨淋巴结,5 例患者（7.15%）发现腋窝以外的前哨淋巴结。淋巴显像确定SLN 的成功率与原发肿瘤病理类型、临床分期、肿瘤部位等因素无显著性相关（均P>0.05）;与注射同位素到显像的时间有显著相关性（均P<0.05）。 术中确定SLN 的成功率在术前淋巴显像成功组与失败组之间有统计学差异（P<0.05）。 结论:乳腺癌SLN 术前淋巴显像在乳腺癌前哨淋巴结活检中具有一定临床价值,99mTc-Sc对乳腺癌前哨淋巴结检测具有较高的检出率和导向性,能较好的指导手术方案的制定,值得临床推广。