{"paper_id":"efbc8758-9efc-41de-839a-cc301e207eda","body_text":"Submit Manuscript | http://medcraveonline.com\nIntroduction\nThe sentinel lymph node (SLN) refers to the first lymph node \nsusceptible to being affected, due to the lymphatic drainage of a \nprimary tumor.1 Initially, it was implanted for penile cancer2 followed \nby melanoma and breast cancer. 3 The lymph node involvement in \ncancer patients is one of the main prognostic factors.\nRegarding pelvic gynecological tumors, the first cancer in which it \nbegan to be implemented was for the vulva and has spread to cervical \nor endometrial cancer. Knowing the affectation or no ganglion besides \nnot only will mark the prognosis 4 determines, but also the adjuvant \ntreatment in these patients. In addition, selective SLN biopsy is \nconsidered the strongest predictor of distant metastasis, particularly \nwhen its affectation is evaluated by immunohistochemistry with \nantibodies against the factor VIII or CD31-related antigen. 5 Thanks \nto this, we will be in the habit of carrying out an adequate therapeutic \nstrategy.\nThe implementation of SLN biopsy has among its objectives \nthe reduction of morbidity associated with lymphadenectomy, 6 \nthe reduction of surgical time, the reduction of intraoperative 7 and \npostoperative complications, such as lymphedema or neuralgia, 8 as \nwell as reducing the costs associated with conventional surgery. All \nthis must be done without entailing a worsening of the prognosis of \nthe target disease.\nAlthough this technique has been accepted as an alternative to \npelvic and para-aortic lymphadenectomy, 9,10 it can be difficult to \nexpose and understand by our patients, especially in cases in which \nit is associated with an increased risk of recurrence. 11 Perhaps these \npatients are not willing to assume a higher risk at the expense of \nreducing the radicality of surgery, something that physicians are. It is \na challenge on the part of the different specialists, to try to improve \nthe results so that SLN does not reduce the treatment of oncological \npatients. For this, it will be essential to make an adequate selection of \npatients. Thus, we will increase our detection capacity in patients with \nearly staging and lower tumor sizes. 5 Before completely replacing \nthe lymphadenectomy, ongoing controlled trials should explore and \nconfirm the additional value of SLN biopsy in both perioperative \nmorbidity and survival. 12 In this review, we intend to perform an \nupdate on the status of the sentinel node within the current gynecology.\nIndications\nIn order to a certain tumor to be susceptible to SLN biopsy, it must \nfollow a consecutive lymphatic drainage through a certain lymph node \nchain. In addition, there must be absence of disease at a distance and \nlymph node involvement both at the clinical level and in the imaging \ntests.13 Also, as a rule the disease should not be locally advanced.\nIn this way, SLN biopsy, whether by laparoscopy, laparotomy or \nrobotic surgery, has proven to be feasible, efficient, safe and imitable.13 \nThis technique SLN biopsy has been shown to be safe and feasible in \nseveral gynecological cancers such as vulvar cancer, cervical cancer \nand endometrial cancer.\nDetection methods\nThere are different tracers used for the detection of SLN. Among \nthem is technetium 99 (Tc99) or methylene blue (MB), with a \ndetection of 66% to 86%. The most recent appearance is the use of \nObstet Gynecol Int J . 2019;10(4):243‒247. 243\n© 2019 Jorge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nThe sentinel node in pelvic gynaecological tumors: \nan updated view\nVolume 10 Issue 3 - 2019\nDuro Gómez Jorge,1 Zuheros Montes José \nDavid,1 Rodríguez Marín Ana Belén,2 Nieto \nEspinar Y olanda,3 Castelo-Branco Camil4\n1Department of Gynecology and Obstetrics, Reina Sofía \nUniversity Hospital, Spain\n2Department of Gynecology and Obstetrics, Hospital San Juan \nde Dios, Spain\n3Department of Gynecology and Obstetrics, Hospital \nUniversitario San Agustín, Spain\n4Clinic Institute of Gynecology, Obstetrics and Neonatology-\nHospital Clinic, Faculty of Medicine-University of Barcelona, \nInstitut d´Investigacions Biomèdiques August Pi i Sunyer \n(IDIBAPS), Spain\nCorrespondence: Camil Castelo-Branco, Institut Clinic of \nGynecology, Obstetrics and Neonatology, Hospital Clinic, \nVillarroel 170, 08036-Barcelona, Spain, T el + 34 93 227 54 36, \nFax + 39 93 227 93 25, Email \nReceived: May 28, 2019 | Published: July 08, 2019\nSummary\nThe sentinel lymph node (SLN) refers to the first lymph node susceptible to being \naffected, due to the lymphatic drainage of a primary tumor. The lymph node involvement \nin cancer patients is one of the main prognostic factors. Without affecting the prognosis \nat any time, the SLN seeks to reduce the morbidity associated with lymphadenectomy, \nreducing surgical time, reducing intraoperative and postoperative complications, such \nas lymphedema or neuralgia and costs associated with conventional surgery. Although \nits use has extensive experience in tumors such as breast, the SG in gynecological \ntumors is still in the early stages. With this review we intend to make a close and \ncurrent view of the use of this technique in malignant tumors of the female genital \ntract.\nKeywords: sentinel lymph node, gynecological tumors, indocyanine green, \ntechnetium-99m, blue dye, fluorescent real-time mapping\nObstetrics & Gynecology International Journal\nReview Article\n Open Access\n\n\nThe sentinel node in pelvic gynaecological tumors: an updated view\n244\nCopyright:\n©2019 Jorge et al.\nCitation: Jorge DG, David ZMJ, Belén RMA, et al. The sentinel node in pelvic gynaecological tumors: an updated view. Obstet Gynecol Int J. 2019;10(4):243‒247. \nDOI: 10.15406/ogij.2019.10.00450\nfluorescent matrices such as indocyanine green (ICG), whose use is \nincreasing within the different protocols.14 ICG together with the near \ninfrared fluorescence has gained a great utility with the advantage of \nproviding real-time images during surgery. It is experimental, the use \nof carbon nanoparticles for labeling remains.15\nThe superiority of MB has been shown together with the tracer \nversus MB only. 16,17 However, ICG has shown greater detection \ncapacity than MB and Tc99m.18 In this prospective study by Holloway \net al.,19 the ICG detected more SLN and more metastases than the MB \nand without safety problems. 19 ICG has an excellent toxicity profile, \nwith higher overall and bilateral detection rates compared to MB and \nhigher bilateral detection rates compared to a combination of Tc-99m \nand blue dye.20,21 There are available studies that even underestimate \nthe use of MB in favor of Tc99 or ICG. 22 Given this, whenever \npossible, the use of ICG should be favored over the other tracers for \nSLN biopsy.23\nOne of the variables to consider, is the time elapsed from the \ninjection of the tracer until its detection. This period is related to the \npossible failure of intraoperative detection. Kushner et al. reported \nthat the best time to detect sentinel lymph nodes with the MB was \n30 minutes after the dye injection. 50 minutes after the injection the \nICG could not be identified. 24 On the other hand, the ICG presents a \ngood detection, from 5 to 60 minutes after its injection. 25 Taking into \nconsideration the time in which the ICG should be detected, its real-\ntime detection achieves better results with a higher bilateral detection \nrate.26 In addition to the time elapsed, it is important to perform \nthe injection of the tracer properly. There are different modalities \ndepending on the type of tumor.27,28\n In addition to those mentioned, there are other factors that may \naffect the detection rate of the SLN and should be considered within \nthe next protocols and studies. Among them and to highlight, the \ndetrimental effect of body mass index (BMI) on ICG detection rates \nas a marker in obese patients.29\nVulva   \nAn adequate diagnostic and therapeutic strategy in the approach to \nvulvar cancer is essential due to survival is better when the treatment \nis rapidly established after diagnosis. The involvement of the inguinal \nor femoral nodes is the main prognostic factor. 30 In this article, we \nreview the published data supporting the SLN biopsy as part of the \nstandard treatment for women with early-stage vulvar cancer and \ndiscuss future considerations for the treatment of this disease.31 \nAdequate selection of patients with squamous cell carcinoma \nof the vulva is essential. 32 The SLN biopsy in vulvar cancer should \nbe limited to stages IB and II of the FIGO which they are unifocal \ntumors, less than 4cm and with clinical and radiological absence of \nlymph node involvement. This way, without affecting the prognosis, \nwe achieved a reduction in operative mortality. 33 In 2008, the first \nGroningen international study on sentinel lymph nodes in vulvar cancer \n(GROINSS-V) demonstrated that the omission of inguino-femoral \nlymphadenectomy is safe in patients with early-stage vulvar cancer \nand negative SLN, simultaneously decreasing morbidity related to the \ntreatment. There are sufficient studies that corroborate the viability, \nsafety and reproducibility of SLN biopsy in these tumors. 34 Some of \nthem, such as Slomovitz, show how SLN biopsy is associated with \na better quality of life than complete lymphadenectomy, is more \ncost-effective than complete lymphadenectomy and achieves a better \npathological evaluation.32\nSomething to highlight in the SLN biopsy in vulvar tumors is the \nultrastaging, since the introduction of this procedure in a standardized \nway, more and lower inguinofemoral ganglion metastases have been \ndiagnosed. The true clinical impact of micrometastases is unknown. \nWhat seems clear is that the larger size of the SLN metastases, make \ngreater the chances of metastasis in non-sentinel lymph nodes and \nthe lower survival rates. In this way, the size of metastases to the \nlymph nodes is included in the last staging system for vulvar cancer. \nHowever, micrometastases have not been included in the staging \nof this type of tumors. Further studies are needed to determine the \nclinical consequences of the size of the SLN metastases.35\nFrom a practical point of view, we have extensive experience in \nthe use of technetium as a tracer. However, there are already studies \nthat have shown that indocyanine green has a similar sensitivity, so it \nshould be evaluated in new protocols in order to can incorporate it into \nour usual practice.36\nIn short, we can see how it has been shown that complete \ninguinofemoral lymphadenectomy is no longer necessary in most \npatients with this disease and there are no excuses for not incorporating \nSLN biopsy in the approach to vulvar cancer. \nCervix  \nCervical cancer is one of the most frequent gynecological tumors \nin young patients, being one of the main causes of death by this reason \nin developed countries. Frequently, at diagnosis the tumor is limited \nto the cervix, around 47% according to OonK. 35 The usual approach \nof these patients goes through radical hysterectomy or trachelectomy \nwith bilateral pelvic lymphadenectomy. 1,37 This has achieved a high \nsurvival at 5 years when it comes to early stages.38,39 The SLN biopsy \nis an appropriate option in this type of patients.40\nThe success of SLN biopsy in cervical cancer will be based on \nan adequate selection of patients in which the tumor is small and is \ntreated with low staging. In general, it should be limited to stages \nIA2 and IBI. The best detection rate is found in tumors below 2cm. 41 \nHowever, it should be considered that currently, it is an experimental \ntechnique with a low implantation rate.42\nTo perform SLN biopsy in cervical cancer, MB can be used with \nor without Tc99. It must be injected into the cervix immediately \nafter the anesthesia had been established. 41 This can be established \nin each quadrant of the cervix, either at 3 and 9 o’clock in the cervix. \nIntraoperatively, MB an be located at a glance.\nThere are studies that compare these markers with indocyanine \ngreen. In patients with early-stage cervical cancer, a higher bilateral \ndetection was confirmed using the IG instead of standard techniques.43 \nIt was also shown in this study by Buda et al. where the conization did \nnot have a significant impact on the detection rate of the lymph nodes \neither with MB+Tc99 or with ICG. In the case of advanced cervical \ncancer (stage IB1>2cm), the detection rate was higher with ICG than \nwith MB+Tc99.\nSo that we can see that ICG is a promising tool for SLN in cervical \ncancer, since it seems less affected by the stage of the disease, with a \nhigher detection rate compared to traditional methods. 42 In addition, \ncurrently the detection of the sentinel node with GI by means of \nrobotics with the da Vinci Xi supposes an added advantage.44\nWe want to highlight an additional advantage of SLN biopsy in \ncervical cancer. This is the possibility of detecting areas outside of \n\nThe sentinel node in pelvic gynaecological tumors: an updated view\n245\nCopyright:\n©2019 Jorge et al.\nCitation: Jorge DG, David ZMJ, Belén RMA, et al. The sentinel node in pelvic gynaecological tumors: an updated view. Obstet Gynecol Int J. 2019;10(4):243‒247. \nDOI: 10.15406/ogij.2019.10.00450\nwhat includes the usual lymphadenectomy, thus being able to have \nadditional histological information. On the contrary, there are some \nscenarios that make more studies necessary, such as its application \nin conservative fertility surgery and in patients with neoadjuvant \nchemotherapy.45 In any case, the superiority of SLN biopsy over PET \nin the detection of lymph node disease has been demonstrated.46,47\nAlthough it is a new technique that will require more studies, \naccording to the National Comprehensive Cancer Network \nguidelines, the BSGC is a viable option for the management of this \ntype of tumors, including it within its therapeutic guidelines. 23,30 In \nconclusion, according to the available evidence, the BSCG is a safe \nprocedure with high detection rate and low false negative rate.44\nEndometrium\nEndometrial cancer is the most frequent cancer of the female \ngenital tract in the US with 6,180 cases in 2017. 36 So, if there is a \ngynecological cancer where the implementation of SLN biopsy is \nmost interesting, it is in this tumor. In patients in initial stages, it is \nvery important to perform a systematic screening of patients without \nmetastasis to lymph nodes to reduce the range of surgical resection, \nand to reduce the incidence of the corresponding complications and \nimprove the quality of life of the patients. 14 SLN biopsy allows the \nreduction of unnecessary lymphadenectomies and reduces the risk of \nunderdiagnosis in patients with metastatic lymph nodes. 48 However, \nthis technique has the difficulty of the double lymphatic drainage \npathway of these tumors. 49 In addition, the different existing types \nmust be considered.50,51 According to the FIRES study, the SLN biopsy \nhas a sensitivity of 97.2% and a negative predictive value of 99.6%.51\nAs in previous cases, several protocols can be used to the SLN \nbiopsy in endometrial cancer. Among them, the Tc 99, the MB or \nthe ICG. ICG has an excellent toxicity profile, with higher overall \nand bilateral detection rates compared to blue dyes, as well as higher \nbilateral detection rates compared to a combination of Tc-99m and \nMB.26,50,51 The ICG in addition to an excellent detection rate shows \na low rate of false negatives This superiority has been revealed even \nwhen we speak of advanced stages (IIIC)51 or high risk types, achieving \na sensitivity, rate of FN and VPN acceptable. In this way, the SLN \nbiopsy with ICG has managed to reduce the total number of complete \nlymphadenectomies, reducing the duration and the additional costs of \nsurgical treatment.52–55\nThe study published by Niikura shows how the tracer injection \nin the cervix is   very sensitive in the detection of SLN metastases in \nearly stage endometrial cancer (stages I and II of FIGO). This is a \nparticularly useful and safe modality when combined with injection \nof blue dye into the uterine body. 56 Controversy exists on the place \nof injection of the tracer. In this regard, the study published by \nRossi shows how cervical ICG injection achieves a higher rate of \nSLN detection and an anatomical lymph node distribution similar \nto hysteroscopic endometrial injection in patients with endometrial \ncancer.57\nIn summary, BSCG with GI is a feasible technique with high \ndiagnostic precision that could eventually displace conventional \nlymphadenectomy in the coming years, thus reducing the associated \nmorbidity and mortality.51\nOvary\nThere are few studies about SLN biopsy in ovarian cancer. \nAnatomy, various histological types and their drainage, or tracer \ninjection, are some of the difficulties that contribute to the limited \nscientific evidence available. An example of this is the study of the \nBuddha where ICG is used for aortic staging in 10 patients with \novarian cancer. In 9 cases the SLN was detected in the aortic region \nafter the injection of the tracer. In 3 cases, SLN were also identified in \nthe common iliac region.58\nCosts  \nThere are few studies that evaluate the costs associated with the use \nof the sentinel lymph node. A sample of this is the study of Buddha, \nwho showed that with SLN biopsy in endometrial cancer there is \na reduction of more than 1000 dollars compared to conventional \nlymphadenectomy. Assuming a total of 66 million dollars less for \nthe total cases of ca. Endometrium in the USA. On the other hand, \nwhen we refer to vulvar cancer, SLN biopsy seems the least expensive \nalternative, mainly due to the great impact of lymphedema associated \nwith conventional surgery on quality of life.59 According to the study \nof van der V orst, with the SLN biopsy in vulvar cancer a reduction \nof 22416 dollars on an annual basis with respect to conventional \nsurgery.60\nWhen comparing the use of the different tracers, the option that the \nICG uses seems to be the most profitable strategy.61,62\nConclusion  \nThe BSGC in gynecological tumors is a current technique that \nmanages to reduce the morbidity and mortality associated with \ntraditional surgery, in addition to achieving a reduction in costs \nassociated with it. This is also achieved, without interfering in the \nprognosis of these patients. New standardized studies are needed to \nreinforce and homogenize this technique so that we can incorporate it \ninto our usual protocols.\nAcknowledgments\nNone.\nConflicts of interest\nThe authors report no declarations of interest.\nReferences\n1. Holman LL, Levenback CF, Frumovitz M. Sentinel lymph \nnode evaluation in women with cervical cancer. J Minim Invasive \nGynecol. 2014;21(4):540–545. \n2. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer. \n1977;39(2):456–466.\n3. Lècuru F, Mathevet P, Querleu D, et al. Bilateral negative sentinel nodes \naccurately predict absence of lymph node metástasis in early cervical \ncancer: Results of the SENTICOL study. J Clin Oncol. 2011;29(13):1686–\n1691.\n4. Fuller AF, Elliott N, Kosloff C, et al. Determinants of increased risk for \nrecurrence in patients undergoing radical hysterectomy for stage IB and \nIIA carcinoma of the cervix. Gynecol Oncol. 1989;33(1):34–39.\n5. Lax SF, Tamussino KF, Lang PF. 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