Sentinel lymph node biopsy in endometrial cancer—Feasibility,safety and lymphatic complications

Objective

To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former.

The role of sentinel lymph node biopsy in early-stage cervical cancer: A systematic review

Pelvic lymphadenectomy procedure is included as part of the standard protocol of radical hysterectomy for women with early-stage cervical cancer (Stage IA to IB1). However, an important sequel to lymphadenectomy procedure is the possible occurrence of lymphedema in the lower abdomen and lower extremities. Previous researches also find that women with lymphedema experience many emotional impacts, including depression, anxiety, and adjustment problems. Only approximately 10% of women with clinical stage IB cervical carcinoma were involved with metastatic disease. If we could better define the relevant lymphatic nodes that must be removed, it is then possible to limit routinely performed lymphadenectomy for regional nodal metastasis in the pelvis, and hence reduce the need for extended surgical staging (para-aortic lymphadenectomy). We systematically reviewed a body of literature and updated available information concerning the current progress on the application of sentinel lymph node biopsy in women with early-stage cervical cancer. All detection methods (preoperative injection of radiocolloid tracer, intraoperative injection of blue dye, or a combination of both techniques) demonstrated reasonable sensitivity (with a few exceptions), high specificity, low false-negative rate and high negative predictive value. The review of the literature in this paper should convince the readers that sentinel lymph node biopsy has the potential to improve the quality of life and the possibility to maintain relapse-free survival for women with cervical cancer. The proper identification of negative sentinel lymph node allows individualized therapy and may preclude the need of lymphadenectomy procedure in most of these women.     

Sentinel Lymph Node Evaluation in Women with Cervical Cancer

Lymph node status is the most important prognosticator of survival in women with early stage cervical cancer. Thus many patients with cervical cancer will undergo pelvic lymphadenectomy as part of the treatment. This procedure is associated with substantial morbidity. Use of the sentinel lymph node technique in women with cervical cancer has the potential to decrease this morbidity. Multiple studies have suggested that sentinel lymph node mapping in these patients is feasible, with excellent detection rates and sensitivity. This review examines the current body of literature about sentinel lymph node biopsy in women with cervical cancer.     

Sentinel node procedures in gynecologic cancers: an overview

The aim of this study was to assess the value of sentinel lymph node procedures in gynecologic cancers. A systematic literature overview, using the PubMed database, was performed. In early stage vulvar, endometrial and cervical cancer, lymph node status is the most important prognostic factor. Lymphadenectomy, performed for adequate staging, is associated with high morbidity rates. Sentinel node procedures hold the promise of adequate staging with less treatment-related morbidity. Sentinel lymph node procedures in patients with early-stage vulvar cancer are associated with low recurrence rates, excellent survival, lower morbidity and shorter hospital stay compared to classical inguinal dissection. Therefore, these procedures should be the standard of care in early-stage unilateral vulvar cancer. Reports on sentinel lymph node procedures in endometrial and cervical cancer are ambiguous. The procedures in these cancers are reported in small studies only. Detection rates vary depending on the used injection sites and the used tracers. Bilateral detection rates are low and are not mentioned by default. Large controlled multi-institutional studies are necessary to evaluate the validity and the prognostic significance of the sentinel lymph node procedures in endometrial and cervical cancer.     

Sentinel lymphatic mapping among women with early-stage cervical cancer: A systematic review

The presence of pelvic lymph node metastases is without doubt the most significant prognostic factor that determines recurrences and survival of women with early-stage cervical cancer. To avoid the underdiagnosis of lymph node metastasis, pelvic lymphadenectomy procedure is routinely performed with radical hysterectomy procedure. However, the pelvic lymphadenectomy procedure may not be necessary in most of these women due to the relatively low incidence of pelvic lymph node metastasis. The removal of large numbers of pelvic lymph nodes could also render non-metastatic irreversible damages for these women, including vessel, nerve, or ureteral injuries; formation of lymphocysts; and lymphedema. Over the past decades, the concept of sentinel lymph node biopsy has emerged as a popular and widespread surgical technique for the evaluation of the pelvic lymph node status in gynecologic malignancies. The histological status of sentinel lymph node should be representative for all other lymph nodes in the regional drainage area. If metastasis is non-existent in the sentinel lymph node, the likelihood of metastatic spread in the remaining regional lymph nodes is very low. Further lymphadenectomy is therefore not necessary for a patient with negative sentinel lymph nodes. Since the uterine cervix has several lymphatic drainage pathways, it is a challenging task to assess the distribution pattern of sentinel lymph nodes in women with early-stage cervical cancer. This review article will adapt the methodology proposed in these studies to systematically review sentinel lymphatic mapping among women with early-stage cervical cancer.     

Status of Sentinel Lymph Node Biopsy in Endometrial Cancer

The role of lymphadenectomy in surgical staging remains one of the biggest controversies in the management of endometrial cancer. The concept of sentinel lymph node biopsy in endometrial cancer has been evaluated for a number of years, with promising sensitivity rates and negative predictive values. The possibility of adequate staging while avoiding systematic lymphadenectomy leads to a significant reduction in the rate of peri- and postoperative morbidity. Nevertheless, the status of sentinel lymph node biopsy in endometrial cancer has not yet been fully elucidated and is variously assessed internationally. According to current European guidelines and recommendations, sentinel lymph node biopsy in endometrial cancer should be performed only in the context of clinical studies. In this review article, the developments of the past decade are explored concisely. In addition, current data regarding the technical aspects, accuracy and prognostic relevance of sentinel lymph node biopsy are explained and evaluated critically.Key words: endometrial cancer, sentinel lymph node, sentinel mapping, ultrastaging     

Sentinel lymph node procedure and uterine cancers

Lymph node metastases in cervical and endometrial cancer are major prognostic factors. Lymph-nodal involvement determines adjuvant therapy. As imagery is not reliable to diagnose lymph node status, pelvic +/- para-aortic lymphadenectomy remains the gold standard. These surgical procedures are, however, responsible for specific morbidity: lymphocele and lymphedema. Sentinel lymph node procedure could avoid lymphadenectomy and their complications in cervical and endometrial cancer with good negative predictive values. We present actual indications, procedure and results of sentinel lymph node procedures in cervical and endometrial cancer.     

Value of the sentinel node biopsy in uterine cancers

In cancer research, regional lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of various cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and recently in breast cancer. In cervical and endometrial cancers, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results and clinical implications of sentinel node procedure in cervical and endometrial cancers.     

Sentinel node detection with radiocolloid lymphatic mapping in early invasive cervical cancer

We assessed the feasibility of sentinel lymph node detection using technicium-99 radiocolloid lymphatic mapping for predicting lymph node metastases in early invasive cervical cancer. Thirty patients with cervical cancer (stages IA2-IIA) underwent preoperative lymphoscintigraphy using technicium-99 intracervical injection and intraoperative lymphatic mapping with a handheld gamma probe. After dissection of the sentinel nodes, the standard procedure of pelvic lymph node dissection and radical hysterectomy was performed as usual. The sentinel node detection rate was 100% (30/30). There were seven (23.3%) cases of microscopic lymph node metastases on pathologic analysis. All of them had sentinel node involvement. Therefore, the sensitivity of sentinel node identification for prediction of lymph node metastases was 100%, and no false negative was found. Preoperative lymphoscintigraphy, coupled with intraoperative lymphatic mapping, located the sentinel nodes accurately in our study patients. This sentinel node detection method appears to be feasible for predicting lymph node metastases.     

Updates in Sentinel Lymph Node Mapping in Gynecologic Cancer

Purpose of Review

The aim of this study is to review the indications, techniques, and outcomes of sentinel lymph node (SLN) mapping in endometrial, cervical, and vulvar cancers.

Recent Findings

In endometrial cancer, the prospective FIRES trial showed that the negative predictive value of SLN mapping was 99.6%. Furthermore, multi-institutional retrospective studies comparing SLN mapping to traditional lymphadenectomy have found comparable survival between the two techniques, in both type 1 and type 2 endometrial cancer. In cervical cancer, randomized data from the SENTICOL-2 study has demonstrated significant reduction in postoperative complications without compromising survival with SLN mapping as compared to SLN mapping and pelvic lymphadenectomy. In vulvar cancer, the GROINS-V-II study protocol was amended to mandate inguinofemoral lymphadenectomy in all patients with SLN macrometastasis greater than 2 mm after unacceptably high rates of groin recurrences were observed on interim analysis. SLN mapping is now included in the treatment guidelines of the National Comprehensive Cancer Network guidelines for endometrial, cervical, and vulvar cancer as an acceptable lymphatic assessment technique in select patients.

Summary

SLN biopsy is a safe and effective alternative to systematic lymphadenectomy for women with early-stage endometrial, cervical, and vulvar cancer. Recent data has validated the excellent sensitivity and negative predictive value of this technique in carefully selected patients, without compromising survival. The use of an algorithm that mandates pathologic ultrastaging on all SLNs, and ipsilateral lymphadenectomy in cases of failed bilateral mapping improves sensitivity and negative predictive value. All suspicious lymph nodes should be resected regardless of the location of the SLN. In patients with vulvar cancer, SLN biopsy is an acceptable standard of care for patients with unifocal tumors, less than 4 cm in largest diameter, and clinically and radiographically negative groin nodes.

     

Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection

OBJECTIVES: We investigated the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled human serum albumin and isosulfan blue dye injection in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. METHODS: Between September 2000 and October 2002, 25 patients with cervical cancer FIGO stage I (n=24) or stage II (n=1) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (technetium-99m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with blue dye and a handheld or laparoscopic gamma probe. Complete pelvic or paraaortic lymphadenectomy was performed in all cases by open surgery or laparoscopic surgery. RESULTS: In 23 evaluable patients, a total of 51 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.21 nodes per patient). Intraoperatively, 61 sentinel lymph nodes were identified, with a mean of 2.52 nodes per patient by gamma probe and a mean of 1.94 nodes per patient after isosulfan blue injection. Forty percent of sentinel nodes were found in the interiliac region and 25% in the external iliac area. Microscopic nodal metastases (four nodes) were confirmed in 12% of cases. All these lymph nodes were previously detected as sentinel lymph nodes. The remaining 419 nodes after pelvic lymphadenectomy were histologically negative. CONCLUSIONS: Sentinel lymph node identification with technetium-99m-labeled nanocolloid combined with blue dye injection is feasible and showed a 100% negative predictive value, and potentially identified women in whom lymph node dissection can be avoided.     

Laparoscopic identification of sentinel lymph node in treatment of invasive cervical cancer

The fundamental prognostic factor in treatment of early cervical cancer is the state of regional lymph nodes. If the first lymphatic node is involved by cancer, the other ones may be affected; otherwise if the first one is free of metastatic cells, the others should not be involved by cancer either. Detection and removal of the lymphatic node called the sentinel lymph node permit to avoid radical lymphadenectomy which is connected with many severe complications. We reported a technique of identification of the sentinel lymph node during laparoscopic radical hysterectomy with pelvic lymphadenectomy in treatment of early invasive cervical cancer with presentation of case history. Identification of sentinel node with its histopathology examination may be essential in women with cervical cancer and potentially identifies women in whom lymph node dissection can be avoided. Laparoscopic lymphadenectomy seems to be equally effective and less invasive in comparison to traditional technique.     

Lymph node mapping and sentinel node detection in carcinoma of the cervix, endometrium and vulva

OBJECTIVES: Validity of the sentinel node concept in patients with cervical, endometrial and vulvar cancer. MATERIAL AND METHODS: 47 cases of FIGO stage I and II cervical cancer, 33 cases of first clinical stage of endometrial cancer and 37 patients with FIGO stage I and II of vulvar cancer. In cervical and vulvar cancer preoperative lymphoscyntygraphy and intraoperative lymphatic mapping with blue dye and handheld gamma probe were performed. In patients with endometrial cancer intraoperative lymphatic mapping with blue dye injected into the cervix and into the uterine corpus subserously were done. In the last 10 cases radiolabeled nannocolloid were administered and the patients underwent preoperative lymphoscyntygraphy and intraoperative radio detection of sentinel node. Sentinel nodes were labeled as blue, radioactive, or blue/radioactive. RESULTS: In cervical cancer sensitivity of the dye and radiocolloid methods was 94%, specificity 100% and negative predictive value 97%. Out of 33 cases of endometrial cancer sentinel node was identified in 29 (87.87%) patients. None of women with histological negative sentinel node had metastases in the rest of lymph nodes resected. Sentinel node was detected in all cases of vulvar cancer. The status of sentinel nodes were representative for all lymph node resected. CONCLUSIONS: Concept of sentinel node may be applied first of all for vulvar cancer and also for cervical and endometrial cancer.     

Sentinel node biopsy in cervical cancer: state-of-the-art in 2007

In cervical cancer, lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy warranting the lymphadenectomy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of solid cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and recently in breast cancer. In cervical cancer, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results and clinical implications of sentinel node procedure in cervical cancer.     

前哨淋巴结在妇科恶性肿瘤中的研究及应用

前哨淋巴结（sentinel lymph node,SLN）是原发恶性肿瘤淋巴转移的第一站,可以通过SLN中是否检测出肿瘤淋巴结转移,推测整个淋巴引流区域的肿瘤转移情况。目前有关SLN的研究已经应用到乳腺癌、黑色素瘤等恶性肿瘤的临床诊疗中。在妇科肿瘤方面,研究者最先在外阴癌中进行了SLN研究,之后在宫颈癌、子宫内膜癌中也相继开展了有关SLN检测及SLN活检（SLNB）的探索研究,并在临床上得到了一定的应用。本文结合相关文献,对国内外子宫内膜癌、宫颈癌、外阴癌和卵巢癌中SLN 的研究现状及目前尚待解决的问题进行简单总结。     

Value of sentinel lymph node procedure in endometrial cancer

In cancer research, regional lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of various cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and in breast cancer. In endometrial cancer, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results, clinical implications and limitations of sentinel node procedure in endometrial cancers.     

Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer

OBJECTIVE: To evaluate fundal injection of blue dye and radiocolloid for lymphatic mapping and sentinel node identification in women with high-risk endometrial cancer. METHODS: At laparotomy, 18 women with high-risk endometrial cancer had isosulfan blue and technitium-99 radiocolloid injected into the uterine fundus subserosally. Sentinel nodes were then identified either by direct observation of blue dye, by radioactive counts using a handheld gamma counter, or by a combination of both methods. The number and location of sentinel node(s) were recorded and compared with the final lymph node specimens after hysterectomy and selective lymphadenectomy. RESULTS: A sentinel node was identified in only 8 (45%) of the cases. Four patients had sentinel nodes only in the pelvis, 2 had sentinel nodes in the pelvis and above the bifurcation of the aorta, and 2 patients had sentinel nodes above the bifurcation of the aorta only. Seven (88%) patients had unilateral drainage of dye and the radiocolloid; the other patient had bilateral drainage. No patients had metastatic disease to sentinel or nonsentinel lymph nodes. CONCLUSIONS: Subserosal fundal injection of blue dye and the radiocolloid is a poor technique for identifying sentinel lymph nodes in patients with high-risk endometrial cancer.     

Role of lymphadenectomy in ovarian cancer

The exact role of lymphadenectomy in the management of ovarian cancer has been the object of controversy during recent years. The International Federation of Obstetrics and Gynecology has indicated that pelvic and para-aortic lymph node sampling is an integral part of the staging system of ovarian cancer. On the other hand the advantage of systematic sampling, resection of bulky nodes only, or no lymphadenectomy in terms of recurrence rate and survival of ovarian cancer patients has not yet been clearly defined. Thanks to the analysis of clinical studies on systematic lymphadenectomy, detailed anatomical studies to assess the location of lymph nodes and lymphatic spread have been recently reported.In this chapter we report the available data on clinical anatomy and pathological assessment of lymph node and lymphatic spread of ovarian cancer metastasis; we also review the clinical data on correlation of lymph node metastasis and disease status. Surgical techniques developed during years of dedication to this procedure are also described. Finally, we review and discuss the actual benefits of lymph node dissection in patients with ovarian cancer, analysing previously reported and ongoing trials.     

Evaluation of sentinel lymph nodes in vulvar,endometrial and cervical cancers

Sentinel lymph node (SLN) biopsies are a sensitive tool in evaluating lymph nodes for multiple cancers, and in some diseases they decrease morbidity in both the short- and long-term. SLN detection in gynecologic malignancies has been studied extensively over the past decade. We review the current literature on SLN dissection in vulvar, endometrial and cervical cancers. Large, well-designed trials in each of the three types of cancer have demonstrated high sensitivity and low false-negative rates when SLN biopsy is performed in the correct patients and with an appropriate technical approach. In all of these cases the addition of ultra-staging to conventional pathology yields increased detection of micrometastatic disease. Biopsy of the sentinel nodes is feasible and safe in early vulvar malignancies, with multiple studies describing low recurrence rates in those women who have with negative SLNs. There does not appear to be a survival benefit to lymphadenectomy over SLN biopsy and quality of life is improved in women undergoing SLN biopsy. Optimal treatment strategies for women with positive nodal biopsies, particularly in cases with micrometastatic disease, remain unclear. Multiple large studies investigating the utility of SLN biopsy in endometrial malignancy have found that sentinel nodal status is a reliable predictor of metastases in women with low-risk disease. Prospective studies are ongoing and suggest sentinel nodal detection may soon become widely accepted as an alternative standard of care for select cases of endometrial cancer. In cervical cancer, SLN biopsy is accurate for diagnosing metastatic disease in early stage tumors (≤ 2 cm diameter or stage ≤ IB2) where the risk of metastasis is low. It is unknown if women who undergo SLN biopsy alone will have different survival outcomes than women who undergo complete lymphadenectomy in these cases. In a specific population of women with vulvar cancer, SLN dissection is an effective and safe alternative to complete dissection. It can be offered as an alternative management strategy in these women. In women who do undergo SLN biopsy, it is associated with improved quality of life. Promising evidence supporting the utility of SLN dissection in endometrial and cervical cancer continues to emerge, and it may soon become a reasonable option for select patients. However, continued research and refinement of appropriate patient selection and long-term follow-up are necessary.     

Sentinel node identification in cervical cancer patients: a feasibility study

OBJECTIVES: According to recommendations, the sentinel node (SN) procedure results causes of less radical treatment and reduction of morbidity. DESIGN: The aim of this study was to determine the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m labelled nanocolloid and blue dye injection in patients with early-stage cervical cancer. MATERIAL AND METHODS: 100 patients with FIGO stage from IB1 to IIA primary carcinoma undergoing radical hysterectomy with pelvic lymphadenectomy have been investigated. RESULTS: 84% of the patients have been diagnosed with at least one-sided SN and 66% of them with two-sided SN. The sentinel detection rates, depending on the stages, were as following: 181-96.6%, IB12-66.7%, IIA-62.5%. Successful identification of SN was less likely in patients with tumors > 2cm (54% of SN) compared with those with tumors < or = 2cm (96% of SN). The false negative rate for the SN procedure was 3% (3/100). In all false negative SNs the primary cervical tumor was above 2cm and there was an isthmus infiltration. SN detection had 86.4% sensitivity, 100% specificity, and 95.3% negative predictive value. CONCLUSION: Sentinel node mapping method for cervical cancer patients undergoing primary surgical therapy is a feasible option. The sentinel node detection rate is relatively high and depends on FIGO stage and the tumor size. The appliance of SN into cervical cancer procedures allows us to refrain from a surgery in favor of radiochemiotherapy, seems to be the right course of action in deciding treatment and may result in fewer postoperative complications rate.