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.     

Intraoperative lymphatic mapping and sentinel lymph node dissection in cervical uterine cancer

Regional lymph node involvement is the most important prognostic indicator in patients with solid tumors. Conventional lymph node dissection has not been shown to affect survical and is often associated with considerable morbidity. Intraoperative lymphatic mapping and sentinel lymph node dissection were therefore designed as a minimally invesive alternative to routine elective lymph node dissection in patients with primary cutaneous melanoma. This study examined whether intraoperative lympatic mapping and sentinel lymph node dissection were accurate in staging patients with cervical 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.     

Sentinel node detection in cervical cancer

BACKGROUND: For superficial tumors such as melanoma, breast, and vulvar cancer, sentinel node detection prevents unnecessary extensive lymph node dissections. Sentinel node detection has not yet proved feasible in tumors, such as cervical cancer, that drain to deep pelvic lymph nodes. TECHNIQUE: We injected technetium-99m colloidal albumin around the tumor allowing preoperative lymphscintigraphy and intraoperative gamma probe detection of sentinel nodes. For visual detection, blue dye was injected at the start of surgery. EXPERIENCE: In six of 10 eligible women who had Wertheim-Meigs operations for cervical cancer stage Ib, one or more sentinel nodes could be detected by scintigraphy. Intraoperative gamma probe detection was successful in eight of ten women, whereas visual detection found sentinel nodes in only four. They were found as far as the common iliac level. One woman had positive lymph nodes, of which one was a sentinel node. CONCLUSION: Identification of sentinel nodes using radionuclide is possible in women with cervical cancer and potentially identifies 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.     

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.     

Sentinellymphadenektomie bei Patientinnen mit Zervixkarzinom

Sentinel lymph node biopsy in women with cervical cancer is an object of current clinical research. Blue dye, technetium-labeled colloids, or their combination are used to detect sentinel lymph nodes. Several studies showed that the best results were achieved through the combination of these agents. Beside the rate of detection the negative predictive value is the most important factor to assess the impact of the sentinel lymph node concept. Incorrect application of the agents used to detect sentinel lymph nodes is one reason for failure of detecting sentinel lymph nodes. False negative detections are seen in patients with grossly metastatic lymph nodes. The detection of sentinel lymph nodes in the parametrial tissue close to the cervix is hampered, as the tissue is either intensively colored or the activity of technetium within the cervix does not allow a detection of smaller deposits of activity within the sentinel lymph nodes. Isolated sentinel lymph nodes can be used for special investigations establishing new prognostic markers. Future studies should clarify which group of patients with cervical cancer will benefit most.     

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.     

Technique et résultats du prélèvement du ganglion sentinelle dans les cancers du col et du corps de l’utérus

In both cervical and endometrial cancers, the lymph node status is an important prognostic factor and a major criterion in decision making concerning an indication for neoadjuvant chemotherapy, which makes the lymph node dissection mandatory. The sentinel lymph node detection has been developed in the aim of reducing surgical morbidity. It appears to constitute a major advance in the management of patients with various malignancies. Its clinical utility became rapidly obvious in malignant melanoma, vulvar cancer and, more recently, breast cancer. In uterine cancers, this procedure is still at the feasibility phase. The present article presents the technical aspects, and the first published results on the potential role of sentinel lymph node detection in cervical or endometrial cancers.     

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.     

Laparoscopic sentinel lymph nodes identification followed by trachelectomy in early stage cervical cancer

The status of regional lymph nodes is the main prognostic factor in diagnosis and treatment of early stage of the cervical cancer. If the first node that drains a tumor site (sentinel node) is not metastatic, other lymph nodes should also be free of the disease. Detection using blue dye and laparoscopic removal of the sentinel lymph nodes let to avoid radical hysterectomy with pelvic limphadenectomy and it is especially useful in young women who want to preserve fertility. We describe a case of a 33- year old woman with invasive cervical cancer who underwent laparoscopic sentinel lymph nodes detection followed by trachelectomy. Thus histopatological examination confirmed no metastasis in removed sentinel lymph nodes, trachelectomy as a minimally invasive procedure was performed.     

Sentinel node mapping in a pregnant woman with cervical cancer: a case report

The possibility of reducing morbidity associated with surgical dissection while maintaining accurate tumor staging is one of the greatest advantages of the sentinel node approach in surgical oncology. The sentinel node mapping has already proven to be useful in melanoma, breast cancer, and vulvar cancer. We report the first case of sentinel node detection by technetium-labeled radiocolloid in a pregnant woman with cervical cancer. The histologic analysis of the operative specimen showed a poorly differentiated squamous carcinoma with metastasis in the sentinel node and a neoplasic embolus in a blood vessel of the placental bed. The lymphatic mapping and sentinel lymph node detection are feasible during pregnancy.     

Laparoscopic detection of sentinel lymph nodes followed by lymph node dissection in patients with early stage cervical cancer

OBJECTIVE: The purpose of this study was to investigate the feasibility of sentinel node detection through laparoscopy in patients with early cervical cancer. Furthermore, the results of laparoscopic pelvic lymph node dissection were studied, validated by subsequent laparotomy. METHODS: Twenty-five patients with early stage cervical cancer who planned to undergo a radical hysterectomy and pelvic lymph node dissection received an intracervical injection of technetium-99m colloidal albumin as well as blue dye. With a laparoscopic gamma probe and with visual detection of blue nodes, the sentinel nodes were identified and separately removed via laparoscopy. If frozen sections of the sentinel nodes were negative, a laparoscopic pelvic lymph node dissection, followed by radical hysterectomy via laparotomy, was performed. If the sentinel nodes showed malignant cells on frozen section, only a laparoscopic lymph node dissection was performed. RESULTS: One or more sentinel nodes could be detected via laparoscopy in 25/25 patients (100%). A sentinel node was found bilaterally in 22/25 patients (88%). Histological positive nodes were detected in 10/25 patients (40%). One patient (11%) had two false negative sentinel nodes in the obturator fossa, whereas a positive lymph node was found in the parametrium removed together with the primary tumor. In seven patients (28%), the planned laparotomy and radical hysterectomy were abandoned because of a positive sentinel node. Bulky lymph nodes were removed through laparotomy in one patient, and in six patients only laparoscopic lymph node dissection and transposition of the ovaries were performed. These patients were treated with chemoradiation. In two patients, a micrometastasis in the sentinel node was demonstrated after surgery. Ninety-two percent of all lymph nodes was retrieved via laparoscopy, confirmed by laparotomy. Detection and removal of the sentinel nodes took 55 +/- 17 min. Together with the complete pelvic lymph node dissection, the procedure lasted 200 +/- 53 min. CONCLUSION: Laparoscopic removal of sentinel nodes in cervical cancer is a feasible technique. If radical hysterectomy is aborted in the case of positive lymph nodes, sentinel node detection via laparoscopy, followed by laparoscopic lymph node dissection, prevents potentially harmful and unnecessary surgery.     

Role of sentinel lymph node biopsy procedure in cervical cancer: a critical point of view

OBJECTIVE: To report our experience about the role of sentinel node biopsy in cervical cancer patients while debating provocatory arguments concerning this procedure. METHODS: From June 2001 to February 2003, patients affected by stage IB(1) cervical cancer were submitted to the sentinel node biopsy procedure. Patients were submitted to lymphoscintigraphy and, subsequently, to laparoscopy in order to locate the sentinel lymph node. RESULTS: Thirty-seven patients were enrolled in the study. Sentinel node(s) was(were) identified with preoperative lymphoscintigraphy in 89% of the patients. Intraoperative detection rate was 70%. During surgery in 31% of the patients, sentinel node was detected bilaterally; in 15%, two sentinel nodes on the same side of the lymphatic vessels were detected. The sentinel node was located at the level of superficial common iliac vessels (26%), external iliac vessels (69%), and superficial obturator vessels (49%). In 77% of the patients, the histologic specimen sent by the surgeon as unique sentinel node contained two or more nodes. Metastatic sentinel nodes were found in 23% of the patients. There was no case with a positive nonsentinel node in the presence of a negative sentinel node. CONCLUSION: Sentinel node detection is a feasible procedure in cervical cancer patients. However, a high percentage of patients is found with bilateral and/or more than one sentinel lymph node. Improvements in detection rate and pathological analysis are needed prior to consider the sentinel node biopsy a routine procedure in cervical cancer patients.     

HPV status in sentinel nodes might be a prognostic factor in cervical cancer

OBJECTIVE: Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the sentinel-node HPV status and pelvic lymph node metastasis in patients with cervical cancer. The patients were followed up for 3 years to evaluate the clinical role of HPV in sentinel nodes as a prognostic factor. METHODS: From August 2001 to July 2003, 57 patients affected by stages IB-IIA cervical cancer had sentinel-node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. Each detected sentinel node was divided into two parts. One part of them was submitted for frozen section examination and the other was submitted for HPV typing by oligonucleotide microarray. After follow-up, we analyzed the outcome of the patients with respect to the influence of sentinel-node HPV. RESULTS: Sentinel nodes were identified in all patients. A total of 79 nodes from 57 patients were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients (17.6%) by frozen section and 11 patients by pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastasis of the pelvic lymph nodes (P<0.05), but showed one false-negative case. HPV DNA was detected in the cervical cancer lesions of 55 patients (96.5%) and 80.0% (44/55) of them were found to have HPV DNA in the sentinel nodes as well. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastasis. Disease recurred in five patients and one of them did not show pelvic lymph node metastasis at surgery. But, all of these patients had HPV in sentinel nodes. The combination of sentinel-node frozen biopsy and HPV typing showed a negative predictive value of 100% in predicting non-metastasis of lymph node and no recurrence of disease. CONCLUSION: Our results suggested the possibility that sentinel-node HPV typing could play a supportive role to reduce the false-negative rate of the sentinel-node biopsy. All of five patients with recurrence had HPV infection in the sentinel nodes. Absence of HPV in sentinel nodes showed reliable negative predictive value for lymph node metastasis and recurrence. Additional study will be needed to confirm the clinical application of the sentinel-node procedure and to determine whether there is a correlation of HPV status of sentinel nodes to lymph node metastasis and recurrence in cervical cancer patients.     

Contribution of the sentinel node procedure to tailoring the radicality of hysterectomy for cervical cancer

OBJECTIVE: The required radicality of hysterectomy for women with early-stage cervical cancer is controversial owing to the risk of severe complications. The aim of this study was to determine the contribution of the sentinel node (SN) procedure to tailoring the radicality of hysterectomy in women with cervical cancer. METHODS: Between April 2001 and December 2005, 54 patients with early-stage or locally advanced cervical cancer underwent laparoscopic sentinel node (SN) biopsy based on combined patent blue and radiocolloid detection. Thirty-nine patients with early-stage cervical cancer underwent a laparoscopic SN procedure with complete pelvic lymphadenectomy and radical hysterectomy. Moreover, 15 women with locally advanced cervical cancer underwent an SN procedure with pelvic and para-aortic lymphadenectomy before concurrent neoadjuvant chemoradiotherapy. RESULTS: The SN detection rate was 83.3%. The detection rate was higher in women with early-stage disease (90%) than in women with more advanced disease (66.6%) (p=0.03). At final histology, 14 metastatic SN were found in 11 (21.3%) of the 54 patients. They comprised macrometastases in 6 SN, micrometastases in 5 SN, and isolated tumour cells in 3 SN. Parametrial involvement with negative sentinel nodes was found in 15.1% of cases. The overall sensitivity, specificity, positive and negative predictive values and accuracy of intraoperative imprint cytology were 20%, 100%, 100%, 79.5% and 80.5%, respectively. Among the 39 women with early cervical cancer, five (12.8%) had parametrial involvement. In univariate analysis, parametrial involvement was significantly associated with large tumour size, advanced-stage disease, positive pelvic lymph nodes and lymphovascular space involvement. Parametrial involvement tended to be associated with positive sentinel nodes. CONCLUSION: These results underline the contribution of the SN procedure to evaluating lymph node status. However, intraoperative imprint cytology appeared poorly accurate, and further histological or biological tools are needed to evaluate SN status and, hence, to tailor the radicality of hysterectomy.     

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.     

Sentinel lymph nodes in early stage cervical cancer

OBJECTIVES: Lymph node status is the most important prognostic factor in cervical cancer. Sentinel lymph node (SLN) procedures have been purported to reduce peri- and postoperative morbidity and operative time. METHODS: All patients with surgically managed clinical FIGO stage IA/B1 cervical cancer underwent SLN followed by pelvic lymphadenectomy with technetium+/-lymphazurin from April 2004 to April 2006. 0.1-0.2 mci of filtered sulfur colloid technetium was injected submucosally into 4 quadrants of the exocervix. Lymphazurin (4cc) was only used if technetium was unsuccessful in identifying bilateral sentinel lymph nodes. Serial microsections at 5 microm intervals were performed and stained intraoperatively. Complete pelvic node dissections were performed in all patients. RESULTS: Forty-two patients underwent SLN, prior to full pelvic lymphadenectomy. Thirty-nine patients were included for the purposes of this study. The incidence in detecting at least one sentinel node was 98% per patient, and 85% per side. Identification of bilateral sentinel lymph nodes was successful in 28 cases (72%). The median number of SLN/side was 2. Three patients were found to have metastatic tumor to lymph nodes. No false negatives were identified. No adverse effects were noted. CONCLUSIONS: SLN biopsy in cervical cancer is feasible to do, with a low false negative rate. We believe SLN should be evaluated per side and not per patient, that a pelvic lymphadenectomy is otherwise required. By following this protocol, the false negative rate can be minimized. The combined reported FN rate in the literature is 1.8%. If our definition is applied, the majority of reported false negative SLN is not actual false negatives.