Sentinel node biopsy: state of the art in cervical cancer staging

Introduction

Cervical cancer, the fourth most prevalent cancer affecting women globally, exhibits a noteworthy disparity in incidence between high-income and low- to middle-income countries, attributable to resource discrepancies⁽¹⁾. High-income countries bear a comparatively smaller load than low- and middle-income countries. The discrepancy arises directly from the disparities in resources. Developed countries have reduced the incidence of cervical cancer through the implementation of immunization and screening programs. Appropriate treatment techniques can be implemented with greater accessibility to staff and technology. But in many developing countries, there are insufficient or nonexistent preventive and treatment programs, due to a lack of infrastructure and funding⁽²⁾. With 527,600 new cases and 265,700 deaths annually, cervical cancer is the second most common malignancy in women and the third greatest cause of cancer-related deaths globally. It continues to be a significant public health concern. Cervical cancer incidence and death rates differ from nation to nation, although they have declined as a result of patients education, screening program adoption, sexual behavior modification, and anti-HPV vaccination. About 34,000 women in Europe were diagnosed with cervical cancer, and 16,000 of them passed away between 2004 and 2007. The fact that over 54% of diagnosed women are under 50 years old should not be underlined⁽³⁾. For early-stage cervical cancer (stages IA to IB1 according to the FIGO 2018 classification), lymph node status is the primary predictor of outcome; however, less than 20% of patients have lymph node involvement at this point⁽⁴⁾. If at least one lymph node is impacted, the five-year survival percentage decreases to 51-78%, from 88-95% in the absence of lymph node involvement^(5,6). The most significant predictor of survival for women with early-stage cervical cancer is the lymph node status⁽⁷⁾. The LACC (Laparoscopic Approach to Cervical Cancer) study, which was recently published, showed that, from an oncological perspective, laparotomy ought to be the preferred surgical technique for treating early-stage cervical cancer⁽⁸⁾. When Herbert Snow suggested in the late 1800s that patients with cutaneous mela­noma should have their clinically normal regional lymph nodes removed electively, he set off a surgical debate that lasted for more than a century. Early removal of “infected” lymph nodes, in his opinion, would enhance patient’s outcomes by preventing further metastasis to distant places⁽⁹⁾.

Methodology

This is a search from electronic databases, including Google Scholar, PubMed, Elsevier, New England Journal of Medicine, Science Direct, Bulletin du cancer and MedicHub, being conducted using as keywords: sentinel node biopsy, cervical cancer, lymph node involvement, and Senticol. The search strategy included controlled vocabulary and keywords to ensure the relevant studies. The inclusion criteria were: full text access, pre-reviewed journal articles, systematic reviews and meta-analyses.

Results

The study by Dumitraşcu et al., 2023, was a review that was completed five years ago at the University Emergency Hospital Bucharest, Romania, including patients with malignant tumors of the cervical region (January 2017 – December 2022). A total of 826 cases of gynecological malignancies were recorded, and 746 operations for malignant tumors were performed. There were 437 conizations, 259 radical hysterectomies with dissection of the lymph nodes, and 50 loop diathermy cervix excisions completed. The impact of the COVID-19 pandemic is indicated by year in the distribution. The total number of radical hysterectomies with lymphadenectomy reduced during the pandemic’s duration, but the percentage of every procedure grew significantly at the same time, according to the data analysis – i.e., compared with an average of 55 radical hysterectomy with lymphadenectomy per year in the three years prior to the pandemic, or 33% of the surgeries performed, there were 25 radical hysterectomies with lymphadenectomy, or 44.6% of all surgeries. Because their cervical cancers were in different stages, 72 of the women who had surgery at the clinic were selected to undergo both a radical hysterectomy and a lymphadenectomy. The average age of the patients was 58.5 years old, and the medium age was 55.8 years old, with the youngest patient being 26 years old and the oldest patient being 75 years old. The histological forms of cancer discovered were endocervical adenocarcinoma in six patients, nonkeratinized squamous cell carcinoma in 40 patients, and keratinized squamous cell carcinoma in 26 patients. The clinical stage was assessed using imaging techniques (CT and MRI) and the patient’s clinical evaluation. A total of 1206 lymph nodes were sampled, with a median of 17.5 removed lymph nodes and 31 having metastases at the point of the study. The characteristic of lymph nodes seen in 22 women was reactive histiocytosis. The 28 patients who underwent primary surgery had a total of 446 nodes evaluated, with a median of 14.5 lymph nodes. The frequency of lymph node dissections and the rates of metastatic lymph node identification were not correlated. Histological evaluation revealed lymph node invasion in two of sample members. Ninety-six individuals (92.86%) were without any metastases. The authors presented a six-year retrospective review of their research, including lymph node imaging evaluation, clinical staging, surgical staging, and histological particularities. The analysis demonstrates how the management approach and addressability evolved during the COVID-19 pandemic. Research on early stage lymph node dissection shows that a higher number of lymph nodes does not always translate into a higher pathologic finding of lymph nodes that have spread to other areas⁽¹⁰⁾.

In the study by Dostálek et al., 2018, for more expansive tumors, a modified method utilizing radiocolloid and blue dye was employed to inject the tracer into the remaining cervical stroma. A total of 350 participants in stages from pT1a to pT2 participated in the trial. In 10%, 8% and 4% of patients, respectively, macrometastases, micrometastases and isolated tumor cells were discovered. In subgroups with tumors below 2 cm, 2-3.9 cm and ≥4 cm, the bilateral detection rate was comparable (79%, 83% and 76%; p=0.460). Among those with bilateral sentinel lymph node (SLN) detection, there were only two cases with false-negative SLN ultrastaging for pelvic lymph node (LN) status. For each of the three subgroups with varying tumor sizes, the false negative rate was extremely low (0.9%, 0.9% and 0.0%; p=0.999). The overall group’s sensitivity was 96%, and it was high in each of the three groups (93%, 93%, 100%; p=0.510). For tumors larger than 2 cm, SLN biopsy is a practical and trustworthy method of LN staging. For bigger tumors, the tracer application technique needs to be adjusted. In 8% of individuals, micrometastases can be found by SLN pathologic ultrastaging. Stage pT1 tumors larger than 2 cm can be detected at the same rate as smaller ones. Regardless of tumor size, the SLN false negative rate for pelvic LN staging is extremely low⁽¹¹⁾.

In the study by Diaz-Feijoo et al., 2019, following SLN biopsy and bilateral pelvic lymphadenectomy, each patient underwent radical hysterectomy. The pathologist examined the SLNs using hematoxylin-eosin staining and immunohistochemistry. The patients (N=128) have been diagnosed with FIGO 2009 stages 1A2, IB1 and IIA1 (early-stage cervical cancer). The entire SLN detection rate (using 99-technecium and blue dye) was 98.4% in 76% of the cases. Nineteen (14.8%) of the patients reported positive SLNs. The results showed that the sensitivity of detection was 79.2% (95% CI; 57.9-92.9), the false negative rate was 20.8% (95% CI; 7.1-42.2), and the negative predictive value was 95.4% (95% CI; 89.6-98.5). It was discovered that five of the patients who presented with tumors bigger than two centimeters with lymphovascular space invasion were false negative cases. Micrometastases were discovered during SLN ultrastaging in three patients (2.3%). With a median follow-up of 8.24 years, the overall survival (OS) at five years was 88.4% (95% CI; 80.9-93.1)⁽¹²⁾.

The study by Lin et al., 2022, comprised 79 patients with cervical cancer in stages IA2, IB1, IB2, IIA1 and IIICp1 who were hospitalized at the Nanfang Hospital’s Department of Gynecology and Obstetrics, between June 2018 and January 2021. Following general anesthesia, the patients received a total of 0.25 mL of carbon nanoparticle injections at the 3 and 9 o’clock positions of the normal cervix. One by one, the initial lymph nodes painted black were removed after being recognized as SLNs. Thirty individuals were chosen at random for pathological ultrastaging who had negative SLNs. A detection rate of 84.8% was achieved by detecting seven SLNs in 67 out of the 79 patients; on average, 5.28 SLNs were found in each patient. Five patients had positive SLNs following the procedure, whereas one patient tested negative for SLN but positive for non-SLN. With a 100% specificity, 16.7% false negative rate, 98.5% accuracy and 98.4% negative predictive value, the SLN biopsy had an 83.3% sensitivity. The distribution of SLN was primarily found in the obturator, external, internal and total iliac regions (15.11%). According to univariate and multivariate studies, tumor size (p=0.033 and p=0.008) and preoperative cervical coning (p=0.045 and p=0.009) were significantly associated. The Kappa test revealed a strong correlation (Kappa value = 0.901, p<0.001) between the status of pelvic lymph node metastases and SLN. No isolated tumor cells or micrometastases were found by pathological ultrastaging detection in 30 patients whose SLN pathological results were negative. In conclusion, nanocarbon tracing cervical cancer SLN is safer and more reliable for patients with preoperative cervical incisions or tumor diameters less than 2 cm. Its application to cervical carcinoma frontal lymph node testing is safe and feasible, with higher detection rates, sensitivity and negative predictive values. The detection rate of isolated tumor cells that have been microtransplanted is not increased by SLN joint pathological hyperparty detection. However, huge-scale, multicenter prospective research studies are still needed to verify the reliability and safety of SLN detection to replace pelvic lymph nodal clearance, and follow-up over time to determine whether lymphatic microtransplantation or isolated tumor cells have a consequence on the overall rate of survival and non-recurrence rate for cervical cancer patients⁽¹³⁾.

In the study by Wang et al., 2022, under anesthesia, 78 patients got a tracer injection into the disease-free cervical tissue block, followed by SLN mapping and a full pelvic lymphadenectomy. Moreover, hematoxylin and eosin staining (HE) was used for a pathological assessment of all the dissected lymph nodes. Also, the immunohistochemical cytokeratin staining micrometastasis revealed the negative SLN on hematoxylin-eosin staining. The objective was to examine the usefulness of SLN mapping in predicting the lymph nodes meta­stases in early-stage cervical cancer, as well as the distribution, detection rate, false negative rate, sensitivity and negative predictive value of the SLN in early-stage cervical cancer by laparoscopy. In cases of cervical cancer, the overall SLN detection rate was 99% (77/78), while the bilateral detection rate was 87% (68/78). For every patient, an average of 12.4 lymph nodes (LN) and 3.6 SLN were removed from each side. The obturator space (61.5%; 343/558) was the primary location of SLN of cervical cancer. This was followed by the external iliac (23.5%; 131/558), common iliac (7.3%; 41/558), parauterine (3.8%; 21/558), internal iliac (2.2%; 12/558), paraabdominal aorta (1.1%; 6/558), and anterior sacral lymphatic drainage area (0.7%; 4/558). Among the 78 cases, 14 instances of LN metastasis were discovered. A total of 38 lymph nodes were positive, comprising 12 non-sentinel LN metastases and 26 SLN metastases. By using pathological ultrastaging and immunohistochemical staining, it was possible to identify one SLN as an isolated tumor cell (ITC) and five SLNs as micrometa­stases (MIC), which made up 23% (6/26) of the positive SLN. In cervical cancer cases, SLN mapping combined with pathological ultrastaging enhanced the prediction of LN metastasis (2/14). The obturator space (65%; 17/26), periuterine region (12%; 3/26), common iliac region (15%; 4/26) and external iliac region (8%; 2/26) are the primary sites of metastatic SLN distribution. The Kappa value was 1 (p<0.001), indicating that the metastasis status of the SLN and retroperitoneal lymph node was fully consistent. This was the consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis. When it came to diagnosing lymph node metastases, the sensitivity, specificity, accuracy, false-negative rate and negative predictive value of SLN biopsy were 100%, 100%, 100%, 0% and 100%, respectively⁽¹⁴⁾.

In the study by Santoro et al., 2020, preoperatively, all patients were diagnosed with early-stage cervical cancer (FIGO stages IA-IIB) and received sentinel lymph node evaluation with OSNA or ultrastaging. Individuals who had sentinel lymph nodes that could only be examined with hematoxylin and eosin for analysis, as well as those with advanced FIGO stages and unique histological subtypes (apart from squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) were not included. Using Fisher’s exact test and the c2 test, clinical data were compared. A k coefficient was calculated in relation to the evaluation of lymph nodes. This retrospective analysis comprised 116 patients in total (63 OSNA and 53 ultrastaging). In all, 140 and 129 sentinel lymph nodes were examined in the ultrastaging and OSNA groups, respectively, and 531 and 605 lymph nodes were excised. Six (11.3%) out of 53 patients in the ultrastaging group and 16 (25.4%) out of 63 patients in the OSNA group were among the 22 patients with metastatic sentinel lymph nodes. Overall, there were seven (5%) of 140 positive SLNs in the ultrastaging group and 21 (16.3%) of 129 in the OSNA group (p=0.0047). Due to comorbidities, pelvic lymphadenectomy was carried out in 26 (49.1%) of the 53 patients in the ultrastaging group and in 34 (54%) of the 63 patients in the OSNA group. Four patients had metastatic non-sentinel lymph nodes: two (7.7%) out of 26 in the ultrastaging group, and two (5.9%) out of 34 in the OSNA group. In the ultrastaging group, there were three (0.6%) of 531 positive pelvic lymph nodes, while in the OSNA group, there were four (0.7%) of 605 positive nodes (p=0.61). Merely two participants in the OSNA group who had negative sentinel lymph nodes also had pelvic lymph node metastases. On the other hand, there were no cases of pelvic lymph node metastases in individuals with OSNA-positive sentinel lymph nodes. None of the individuals in the ultrastaging group who had negative sentinel lymph nodes also had illness that had spread to additional pelvic lymph nodes⁽¹⁵⁾.

In the study by Balaya et al., 2020, 405 patients were included in the research; 381 patients (94.1%) had unilateral and 326 patients (80.5%) had bilateral SLNs found on the pelvis. The age range for the mean was 22-28.5 years old. The majority of patients (81.3%) had squamous cell carcinoma, with an IB1 pathologic FIGO 2018 stage. Ninety percent of the surgeries were done using a minimally invasive technique on 368 individuals. According to multivariate analysis, there was a significant correlation between decreased SBM rate and age ≥70 years old (ORa=0.02; 95% CI; 0.001-0.28; p=0.004), tumor size bigger than 20 mm (ORa=0.46; 95% CI; 0.21-0.99; p=0.048), and a Body Mass Index higher than 30 kg/m² (ORa=0.28; 95% CI; 0.12-0.65; p=0.003) among these factors. Age ≥70 years old (ORa=0.02; 95% CI; 0.001-0.28; p=0.004), tumor size greater than 20 mm (ORa=0.46; 95% CI; 0.21-0.99; p=0.048) and a Body Mass Index greater than 30 kg/m² (ORa=0.28; 95% CI; 0.12-0.65; p=0.003) were all significantly linked with decreased SBM rate. SBM rate was considerably higher in SENTICOL II (2009-2012) compared to SENTICOL I (2005-2007) (ORa=2.6; 95% CI; 1.23-5.51; p=0.01) and in high-skills centers (more than five patients per year) (ORa=8.05; 95% CI; 2.06-31.50; p=0.003)⁽³²⁾. Greater familiarity with the SLN biopsy technique enhances bilateral SLN detection in early-stage cervical cancer patients. However, individuals older than 70, those with a BMI less than 30 kg/m² and those with bigger tumors measuring more than 20 mm have poorer bilateral SLN detection rates. Sentinel lymph node biopsy requires bilateral detection in order to improve sensitivity and lower the false-negative rate. Obesity may reduce the ability to detect sentinel lymph nodes bilaterally. Patients older than 70 had a decreased rate of bilateral sentinel lymph node detection. When a tumor is bigger than 20 mm, it is more common for the sentinel lymph nodes to not be detected bilaterally. Sentinel lymph node detection was improved by experience and increased surgical proficiency⁽¹⁶⁾.

SENTICOL III

SENTICOL III is a multinational, single-blind, randomized, multicenter study. For patients with negative sentinel lymph nodes, it will evaluate the disease-free survival and health-related quality of life between sentinel lymph node biopsy alone and SLN biopsy plus pelvic lymphadenectomy. The co-primary goal of the primary goal is to link the quality of life connected to health and the absence of sickness. In contrast to sentinel lymph node plus pelvic lymph node dissection, the hypothesis states that disease-free survival is noninferior and that health-related quality of life is better following SLN. The secondary goals include overall survival, recurrence-free survival, cost analysis in France, lymphatic and lower limb complications, assessment of mapping with indocyanine green, surgical mortality and morbidity, other aspects of health-related quality of life, and the outcome of pN1 patients through a particular cohort (considering the size of the metastasis). A sentinel lymph node biopsy will be performed on patients according to a rigid protocol. The injection will be given the day before surgery for those who will include the use of a radiotracer. Both lengthy and brief protocols are accepted. Patients undergoing radiotracer mapping must have preoperative imaging; SPECT-CT is the preferred modality, while lymphoscintigram is also appropriate. Adhesiolysis will be carried out if required, and access will be acquired using laparoscopic, robotic or open methods. The abdominal incision can be made either before or after the cervical injection. It is necessary to administer at least two deep injections at 3 and 9 o’clock (extra injections are permitted). Isotope + ICG, isotope + blue dye, isotope alone, or isotope + ICG can all be used for detection. Just using blue dye is prohibited⁽¹⁷⁾. With no difference in the pathological confirmation of nodal tissue between the two mapping substances, indocyanine green dye with near-infrared fluorescence imaging revealed more sentinel nodes than isosulfan blue dye in women with cervical and uterine malignancies⁽¹⁸⁾.

Discussion

Complete lymph node dissection was very controversial, because it is a major procedure that carries a high risk of serious complications⁽¹⁹⁾. For women with early-stage cervical cancer, the most common operations performed are total pelvic lymphadenectomies and radical hysterectomy. Sentinel lymph node mapping, which attempts to precisely assess nodal expansion and reduce lymphatic morbidity, may be a viable substitute for conventional pelvic lymphadenectomy. The sentinel lymph node is the first lymph node that cancer cells are likely to spread to from a primary tumor. Nowadays, the standard of care for several cancers, such as breast cancer and melanoma, is sentinel lymph node biopsy. Numerous studies attest to the feasibility of sentinel lymph node examination for women with early-stage cervical cancer, with great detection rates and sensitivity⁽²⁰⁾. Systematic pelvic lymph node dissection (PLND) has been gradually replaced with sentinel lymph node biopsy, which is a more accurate way to assess lymph nodal involvement in early-stage cervical cancer⁽²¹⁾. Reduced-radical lymph node dissection lowers the morbidity associated with PLND, particularly the chance of lower-leg lymphoedema, which has a serious negative impact on the quality of life of the patient. By improving the detection of tumor low-volume (single tumor cells and micrometastases), SLN biopsy facilitates node ultrastaging and offers additional histological information. Moreover, by locating nodes outside of typical lymphadenectomy regions, SLN biopsy offers precise anatomical information on the pelvic lymphatic drainage system⁽²²⁾. SLN biopsy is not yet the gold standard, despite new international guidelines recommending it in addition to PLND; this is because there is a dearth of prospective data, particularly regarding long-term oncological safety. Certain topics, such as the impact of micrometastases on prognosis and the poor accuracy of intraoperative SLN status evaluation by frozen section, are still up for debate. Despite being regarded as a substitute for PLND in worldwide standards, SLN biopsy is not currently the gold standard on its own because there is a dearth of prospective data about long-term oncological safety. SENTIX, PHENIX and SENTICOL III – three current prospective trials – will most likely provide an answer to these questions^(23,24). A well-established risk factor for lower limb lymphoedema is the number of sampled nodes, as does the excision of the circumflex iliac lymph nodes or the lateral external iliac chain. Thus, the risk of lower limb lymphoedema should be decreased by SLN biopsy, which is based on focused and restricted sampling of nodes, primarily found in the interiliac region⁽²⁵⁾. More lymphatic morbidities could result from more thorough nodal dissection⁽²⁶⁾.

1. Technique

It seems that SLN biopsy by itself is a safe way to evaluate the lymph nodes in women having surgical staging⁽²⁷⁾.The external iliac, internal iliac, interiliac, hypogastric, obturator, and bifurcation areas were the most often observed localizations of SLNs⁽²⁸⁾. Unconventional drainage locations, such as the common iliac, para-aortic, presacral, cardinal ligament, and parametrial regions have been reported to harbor certain SLNs. Numerous investigations have demonstrated the feasibility and good sensitivity and detection rates of SLN mapping in these patients. Although technetium-99 and blue dye combined detection has been utilized extensively, there has recently been a rise in interest in the use of fluorescent dies, such as indocyanine green (ICG), which would enhance single-photon nuclear (SLN) detection. The overall and bilateral sentinel lymph node detection rates have improved with the use of ICG dye in place of methylene blue. The NCCN guidelines for stage IB1 illness (tumors less than 2 cm) now include SLNB⁽²⁹⁾. The sentinel lymph node is found using a combination approach that includes the injection of a radioisotope before the intervention and a dye or fluorophore injection shortly after the induction of anesthesia. The sensitivity of sentinel lymph node detection is increased by this combination approach. Metastable technetium-99 is the radioisotope that is employed in conjunction with colloidal rhenium sulfide, which has the ability to migrate lymphatics. There are two alternative injection protocols: short and lengthy. When following a lengthy protocol, a dose of 120 MBq is given the day before the procedure, with less than 15 hours to spare before the operating room. If the treatment is brief, a dose that is lowered to 60 MBq is given on the same day. The nuclear medicine department must validate the injection circuit. Most of the time, injecting the tracer near a conization scar or the tumor’s edge is simple. Submucosal injections are carried out in healthy tissue along the tumor’s perimeter at two sites (3 and 9 o’clock) or at four points (0, 3, 6 and 9 o’clock), a few millimeters deep, using a 22-gauge needle. A few hours following the injection, a lymphoscintigraphy is carried out using anterior and lateral pictures (one to three hours in the event of a short protocol or three to five hours in the case of a long protocol). The performance of the diagnostics or the detection rate do not appear to be impacted by these various delays. The surgeon receives the photos, so they can direct the surgical process. The injection procedures for any one are the same as those for the isotopes. At two or four sites, one or two milliliters can be injected. One can inject deeply and superficially, or just superficially. In order to prevent the cervix and any surrounding tissues from turning blue or green and making subsequent dissections more difficult, it is not advised to inject a higher volume. Since Patented Blue is visible with the unaided eye, no special equipment is needed; however, the isotope needs a manual detecting probe, a video system with an infrared source and special optic for open or laparoscopic surgery, and an ICG. In order to confirm that there are no suspicious macroscopic lymph nodes, the first step is to find the migration of either patent blue or indocyanine green in the lymphatic channels with closed peritoneum in the pelvic, sacral and lumbo-aortic areas. This condition must be exceptional with the preoperative imaging assessment. Near the iliac bifurcation, in the external iliac regions, it is where most lymph nodes are found. Thus, we are searching for a colorful pathway to enter this region or a noticeable “hot” or colored lymph node beneath the peritoneum. In order to explore the parametrium and pelvic areas, the second stage entails opening the peritoneum opposite the external iliac arteries and developing the ilio-obturator and paravesical fossae. Every landmark has to be recognized: ureters, obturator nerves, umbilical arteries, and external iliac vessels. This dissection is crucial in order to look for every potential afferent channel and confirm that there isn’t a ganglion upstream of the ganglion that was first discovered. SLN mapping appears to be crucial in the case of early-stage cervical cancer. Certain SLN development sites – such as paraaortic and presacral lymph nodes – are excluded in normal pelvic lymphadenectomy for early cervical cancer, and some are easily overlooked in postoperative pathological exams. However, these lymph nodes show up as the SLNs for cervical cancer, and in some cases, they even show up as the only SLN. This suggests that routinely dissecting lymph nodes in the same locations for each patient may miss some crucial first-stop lymph nodes or even those that have already advanced.  By tracking the dye’s migration, this method enables the early observation of the cervix’s lymphatic outflow through the parametrium. In order to avoid sampling a secondary sentinel lymph node and missing the real sentinel lymph node, no lymph node should be sampled prior to observing an afferent channel. While sampling additional sentinel lymph nodes can lower the chance of false negatives, only the first node in the chain that accurately corresponds to the sentinel lymph node should be sampled out of all the nodes found intraoperatively. Bilateral detection – or at least one sentinel lymph node on each side – should be the goal, regardless of the detection method employed. In cases when there is unilateral detection, it is imperative to examine and maybe open the fossae completely in order to look for a canal or lymph node that may have been missed at first and ended up in an unusual location. It requires precision and patience. When utilizing patent blue, the appearance of a blue node or a node with a blue afferent lymphatic channel designates a sentinel node. Similar to this, after the system is activated in ICG, a sentinel lymph node or its afferent channel glows green. Thirdly, with closed peritoneum in the common iliac, sacral and aortic-caval territories, the exploration of other regions is pursued. It is crucial to avoid taking the so-called “secondary” lymph nodes, which are efferently attached to an external iliac sentinel lymph node. Conversely, our attention has to be directed toward the identification of a channel accessory that connects the sacral or aortic regions directly to the medial edge of the utero ligament sacral. The detected sentinel node(s) undergo sampling voluntarily and forwarded to pathology for review by outside experts. It is particularly noteworthy when the external iliac level sentinel lymph node is not found⁽³¹⁾. The simultaneous pararectal fossa incision allows for the full identification of the parameter and the start of the radical hysterectomy, which often comes after the sentinel lymph node has been found. Lastly, the absence of a sentinel lymph node in the parameters must be verified before doing the prolonged hysterectomy. Maintaining these intervals guarantees the technique’s repeatability and dependability. The detection and administration of cervical injections must have a learning curve. It can be accomplished either with the assistance of a trained operator, or by methodically combining a pelvic dissection following the identification of sentinel lymph nodes^(30,31).

2. Ultrastaging

The diagnosis of isolated tumor cells (ITC; less than 0.2 mm) and micrometastases (0.2-2 mm) is made possible by ultrastaging, which combines the use of serial sections with immunohistochemistry. These tumor cells are more rarely found by routine techniques that involve one section per lymph node and standard staining. Because of this, the SLN-ultrastaging association had a higher sensitivity than the reference approaches, allowing for the diagnosis of 15% of patients with lymph node involvement in addition, especially when sentinel lymph node detection was bilateral. The identification of micrometastatic sentinel lymph nodes, which are linked to macrometastatic non-sentinel lymph nodes and which may have gone unnoticed, increases sensitivity by preventing patients from receiving the necessary extra therapy and from receiving an underdiagnosis of N1 status⁽³²⁾.

3. Advantages and disadvantages

Despite some intriguing results, pelvic node dissection is currently used in conjunction with SLNB, not alone. In fact, doubts have been expressed concerning the precision of intraoperative detection, the capacity to identify micrometastases, and the scant data from prospective investigations. In 395 patients, the SENTIX trial assessed intraoperative SLN frozen section and SLNB without pelvic node dissection. While SLN pathological exams were highly detective for node staging, around 50% of problematic nodes were missed by the intraoperative SLN frozen section. Patients with early-stage cervical cancer are being enrolled in the SENTICOL III and PHENIX ongoing trials. The SENTICOL II study demonstrated the reduced morbidity of SLNB alone; the SENTICOL III trial comes after it⁽³³⁾. The type of histological method (frozen section versus imprint cytology), the size of sentinel node metastasis (macro- versus micrometastases), and the time required for this technique are the three main drawbacks of intraoperative testing. The secondary reinterventions necessary to finish the dissection of the axillary lymph nodes are all under these limitations^(34,35). There are related morbidities, such as blood loss, neurological problems and lymphedema^(36,37). 

4. Contraindications

The sentinel node biopsy is not suitable for every patient, much as any surgical technique. A number of circumstances, including tumor biologic properties, in addition to host considerations, could negatively affect the procedure’s success rate. Nonetheless, a relatively small percentage of patients are ineligible or have many risk factors that could jeopardize the success of the SLNB⁽³⁸⁾. However, both the surgeons doing SLNB and these patients must be successfully recognized, instructed and admonished. Patients who have an axilla that is clinically positive (N1) are not eligible to have the surgery. It has been proposed that, in these situations, tumor cells invading the lymph vessels may obstruct the dye’s or the radiocolloid agent’s passage. This might make it impossible to identify the real sentinel node or nodes, which would lead to process failure or erroneous negative results⁽³⁹⁾. Up to 2.7% of patients get allergic responses during surgery as a result of the blue dyes used for lymphatic mapping in sentinel lymph node biopsy. Methylene blue, isosulfan blue and patent blue are some of these agents. Other names for the sodium salt of patent blue are: acid blue 1, food blue 3, patent blue VF, and sulfan blue. The exact significance of prior biopsy remains unclear, because many of the significant prospective large-series research on SLNB omitted individuals who had undergone axillary surgery or excisional biopsy in the past. Sentinel lymph node biopsy appears to be possible in all patient ages; however, as age and BMI increase, the procedure’s detection rate may be affected⁽⁴⁰⁾.

Conclusions

It is well evident, from the studies mentioned before, that SLN mapping and biopsy are practical and very sensitive in identifying patients who have already developed metastases when it comes to early-stage cervical cancer. It has fewer disadvantages compared to total lymphadenectomy, although it has historically been the recommended approach to staging cervical cancer. Sentinel lymph node mapping must be replaced as the gold standard technique in this modern age of minimally invasive procedures^(41-44).  

Corresponding author: Meenakshi Dileep, e-mail: meenakshi.dileep@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.