Clinical application of the sentinel lymph node technique in early ovarian cancer: a pilot study

IntroductionThere is limited evidence favoring the use of the sentinel lymph node technique in ovarian cancer, and no standardized approach has been studied. The objective of the present pilot study is to determine the feasibility of the sentinel lymph node technique by applying a clinical algorithm.MethodsPatients with confirmed ovarian cancer were included. 99mTc and indocyanine green were injected into the ovarian and infundubulo-pelvic ligament stump. A gamma probe and near-infrared fluorescence imaging were used for sentinel lymph node detection.ResultsThe sentinel lymph node technique was performed in ten patients with a detection rate in the pelvic and/or para-aortic region of 100%. The tracer distribution rates of sentinel lymph nodes in the pelvic and para-aortic regions were 87.5% and 70%, respectively.ConclusionThe detection of sentinel lymph nodes in early-stage ovarian cancer appears to be achievable. Based on these results, a clinical trial entitled SENTOV (SENtinel lymph node Technique in OVarian cancer) will be performed.

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Sentinel-node biopsy in early stage ovarian cancer: a prospective multicentre study (SELLY)

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000886 ◽

2019 ◽

Vol 29 (9) ◽

pp. 1437-1439

Author(s):

Giovanni Scambia ◽

Camilla Nero ◽

Stefano Uccella ◽

Enrico Vizza ◽

Fabio Ghezzi ◽

...

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Indocyanine Green ◽

Epithelial Ovarian Cancer ◽

Sample Size ◽

Early Stage ◽

Sentinel Lymph Nodes ◽

Exclusion Criteria

BackgroundSystematic para-aortic and bilateral pelvic lymphadenectomy is included in the standard comprehensive surgical staging in presumed early epithelial ovarian cancer. No prospective randomized evidence suggests it has potential therapeutic value, and related morbidity is not negligible.Primary Objective(s)To assess sensitivity, safety, and feasibility of the sentinel lymph node technique in identifying the presence of lymph node metastases in patients with early stage epithelial ovarian cancer.Study HypothesisSentinel lymph node detection with indocyanine green can accurately predict nodal status in a cohort of women with early stage epithelial ovarian cancer.Trial DesignThe SELLY trial is a prospective phase II interventional multicenter study.Major Inclusion/Exclusion CriteriaInclusion criteria: Eastern Cooperative Oncology Group 0–1, apparent International Federation of Gynecology and Obstetrics (FIGO) stage I-II, histologically proven epithelial ovarian cancer.Exclusion criteria: evidence of carcinomatosis, mucinous only at definitive histology.Endpoint(s)Primary endpoint is sensitivity (true positive rate). Secondary endpoints include safety (complications rate of the procedure) and feasibility.Sample SizeAssuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (ie, the maximum marginal error) d=5%, and a type I error α=0.05, a sample size of 160 patients is needed to test the general hypothesis (ie, to answer whether sentinel lymph nodes identified with indocyanine green can accurately predict nodal status at histology of patients with apparently early epithelial ovarian cancer). Assuming a drop-out rate of 10%, a total of 176 patients will be enrolled in the study.Estimated Dates for Completing Accrual and Presenting ResultsThe accrual should be completed by December 2020 and results should be presented by March 2021.Trial RegistrationThe trial is registered at clinicaltrials.gov (NCT03563781).

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Sentinel lymph node technique in early-stage ovarian cancer (SENTOV): a phase II clinical trial

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001289 ◽

2020 ◽

Vol 30 (9) ◽

pp. 1390-1396 ◽

Cited By ~ 2

Author(s):

Victor Lago ◽

Pilar Bello ◽

Beatriz Montero ◽

Luis Matute ◽

Pablo Padilla-Iserte ◽

...

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Adverse Events ◽

Lymph Nodes ◽

Early Stage ◽

Sentinel Lymph Nodes ◽

Link Type ◽

The Mean ◽

Early Stage Ovarian Cancer

ObjectiveEarly-stage ovarian cancer might represent an ideal disease scenario for sentinel lymph node application. Nevertheless, the published experience seems to be limited. Our objective was to assess the feasibility and safety concerns of sentinel lymph node biopsy in patients with clinical stage I–II ovarian cancer.MethodsWe conducted a prospective cohort study of 20 patients with histologically confirmed ovarian cancer. 99mTc and indocyanine green were injected into both the utero-ovarian and infundibulopelvic ligament stump, if they were present, during surgical staging. An intraoperative gamma probe and near-infrared fluorescence imaging were used to detect the sentinel lymph nodes. Inclusion criteria included: >18 years of age, suspicious adnexal mass (unilateral or bilateral) at ultrasound and CT imaging or confirmed ovarian tumor after previous surgery (unilateral or bilateral salpingo-oophorectomy with or without hysterectomy). Adverse events were recorded through postoperative day 30. The primary trial end point was to report adverse events related to the technique, including the use of 99mTc and ICG intraperitoneally, as well as the feasibility of the technique.ResultsA total of 20 patients were included in the analysis. Sentinel lymph nodes were detected in 14/15 (93%) pelvic and all 20 (100%) para-aortic regions. Five patients did not have utero-ovarian injection because of prior hysterectomy. The mean time from injection to sentinel lymph node resection was 53±15 min (range; 30–80). The mean number of harvested sentinel lymph nodes was 2.2±1.5 (range; 0–5) lymph nodes in the pelvis and 3.3±1.8 (range; 1–7) lymph nodes in the para-aortic region. There were no adverse intraoperative events, nor any within the 30 days of follow-up related with the technique.ConclusionSentinel lymph node mapping in early-stage ovarian cancer is feasible without major intraoperative or < 30 days safety concerns. (NCT03452982).Trial registration numberClinicalTrials.gov, NCT03452982.

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Novel quinoline-based near-infrared fluorescent bioimaging probe, KSNP117, for sentinel lymph node mapping

Journal of Materials Chemistry B ◽

10.1039/d1tb00568e ◽

2021 ◽

Author(s):

Ahmed A. Elbatrawy ◽

Da Sol Lee ◽

Sang Bong Lee ◽

Hui-Jeon Jeon ◽

Sijoon Lee ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Near Infrared ◽

High Sensitivity ◽

Sentinel Lymph Node Mapping ◽

Sentinel Lymph Nodes ◽

Fluorescent Imaging ◽

Imaging Agents ◽

Lymph Node Mapping

Near-infrared (NIR) fluorescent imaging agents with biocompatibility and high sensitivity are urgently required for the accurate detection of sentinel lymph nodes (SLNs). Herein, we report the design of a novel...

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Standard ultrastaging compared to one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastases in early stage cervical cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001710 ◽

2020 ◽

Vol 30 (12) ◽

pp. 1871-1877

Author(s):

Angela Santoro ◽

Giuseppe Angelico ◽

Frediano Inzani ◽

Damiano Arciuolo ◽

Saveria Spadola ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Early Stage ◽

Sentinel Lymph Nodes ◽

Nucleic Acid Amplification ◽

Lymph Node Status ◽

Pelvic Lymph Nodes ◽

Lymph Node Assessment ◽

Node Metastases

ObjectiveWe compared ultrastaging and one-step nucleic acid amplification (OSNA) examination of sentinel lymph nodes in two homogeneous patient populations diagnosed with early stage cervical cancer. The primary aim of our study was to evaluate the rate and type of sentinel lymph node metastases detected by ultrastaging and OSNA assay. Secondary aims were to define the sensitivity and the negative predictive value of sentinel lymph node biopsy assessed with OSNA and ultrastaging and to define the role of sentinel lymph node assessment in predicting non-sentinel lymph node status.MethodsConsecutive patients who underwent surgery (radical hysterectomy or trachelectomy or cervical conization) at our institution, between January 2018 and March 2020, were enrolled. All patients had a preoperative diagnosis of early-stage cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) 2018 stages IA–IIB) and underwent sentinel lymph node assessment with ultrastaging or OSNA. Patients with advanced FIGO stages and special histology subtypes (other than squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) or patients with sentinel lymph nodes analyzed only with hematoxylin and eosin were excluded. Clinical data were compared using the χ2 test and Fisher’s exact test. A κ coefficient was determined with respect to lymph node assessment. A p value <0.05 was considered statistically significant.ResultsA total of 116 patients were included in this retrospective analysis (53 ultrastaging, 63 OSNA). Overall, 531 and 605 lymph nodes were removed in the ultrastaging and OSNA groups, respectively, and 140 and 129 sentinel lymph nodes were analyzed in the ultrastaging and OSNA groups, respectively. 22 patients had metastatic sentinel lymph nodes: 6 (11.3%) of 53 patients in the ultrastaging group and 16 (25.4%) of 63 patients in the OSNA group. The total amount of positive SLNs was 7 (5%) of 140 in the ultrastaging group and 21 (16.3%) of 129 in the OSNA group, respectively (p=0.0047). Pelvic lymphadenectomy was performed in 26 (49.1%) of 53 patients in the ultrastaging group and in 34 (54%) of 63 patients in the OSNA group due to comorbidities. Metastatic non-sentinel lymph nodes were found in 4 patients: 2 (7.7%) of 26 patients in the ultrastaging group and 2 (5.9%) of 34 patients in the OSNA group, respectively. The total amount of positive pelvic lymph nodes was 3 (0.6%) of 531 in the ultrastaging group and 4 (0.7%) of 605 in the OSNA group (p=0.61). In the OSNA group, only 2 patients with negative sentinel lymph nodes had metastatic disease in the pelvic lymph nodes. By contrast, no patients with OSNA-positive sentinel lymph nodes had metastases in the pelvic lymph nodes. In the ultrastaging group, all patients with negative sentinel lymph nodes did not have metastatic disease in other pelvic lymph nodes.ConclusionsOSNA assessment of sentinel lymph nodes was associated with a negative predictive value of 91% but poor reliability in detecting node metastases in non-sentinel pelvic lymph nodes. Of note, the ultrastaging protocol revealed higher sensitivity and more reliability in predicting pelvic non-sentinel lymph node status.

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Sentinel lymph node identification in early stage ovarian cancer: is it still possible after prior tumor resection?

Journal of Ovarian Research ◽

10.1186/s13048-021-00887-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Pim Laven ◽

Roy Kruitwagen ◽

Petra Zusterzeel ◽

Brigitte Slangen ◽

Toon van Gorp ◽

...

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Sentinel Node ◽

Early Stage ◽

Frozen Section ◽

Gamma Probe ◽

Tumor Resection ◽

Blue Dye ◽

Sentinel Nodes

Abstract Objective Sentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian tumor has already been resected with injection of the tracer into the ovarian ligaments stumps, i.e. in the event that a frozen section confirms malignancy. Methods Patients who underwent laparotomy with frozen section confirming an ovarian malignancy, and those who underwent a second staging laparotomy after prior resection of a malignant ovarian mass, were included. Blue dye and a radioactive isotope were injected in the stumps of the ligamentum ovarium proprium and the ligamentum infundibulo-pelvicum. After an interval of at least 15-min, the sentinel node(s) were identified using either the gamma-probe and / or blue dye. Results A total of 11 patients were included in the study, the sentinel node (SLN) procedure was completed in all 11 patients. At least one SLN was identified in 3 patients, resulting in a rather low detection rate of 27,3%. Conclusion In this study we showed that SLN procedure after (previous) resection of the tumor seems inferior to detect sentinel nodes when compared to injection of the tracer in the ovarian ligaments before tumor resection. Trial registration NCT02540551

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Hemosiderin: a new marker for sentinel lymph node identification

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502009000600002 ◽

2009 ◽

Vol 24 (6) ◽

pp. 432-436 ◽

Cited By ~ 12

Author(s):

Luiz Gonzaga Porto Pinheiro ◽

Renato Santos de Oliveira Filho ◽

Paulo Henrique Diógenes Vasques ◽

Pedro Henrique de Oliveira Filgueira ◽

Douglas Henning Pinheiro Aragão ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Breast Biopsy ◽

Gamma Probe ◽

Sentinel Lymph Nodes ◽

Patent Blue ◽

Sentinel Lymph Node Identification ◽

Lymphatic Duct ◽

The Right

PURPOSE: To evaluate and present our initial results of a new marker (hemosiderin) for mammary sentinel lymph node identification in an experimental model. METHODS: Skins mapped like a lymphatic duct draining to the axilla in patients submitted to breast biopsy, in our mastology service, stimulated us to try it in an animal model (female dogs). Our theory was that some blood derivate (hemosiderin) was captured by macrophages and accessed the lymphatic ducts in direction to the axilla. Six female dogs of no defined race were studied. We injected 0,2 ml of technetium on both superior mammary glands. After ten minutes, a 2,5 ml solution of hemolized blood (hemosiderin) from the own animal was injected in the subareolar lymphatic plexus on the left superior mammary gland and 2,5 ml of patent blue concomitantly and equally on the contralateral gland. Ten minutes after, incisions on both axilas were made to search, through the lymphatic mapping and a gamma probe, the sentinel lymph nodes. RESULTS: Seven brown sentinel lymph nodes were indentified and also radiomarked on the left axilla. Six blue sentinel lymph nodes were identified and also radiomarked on the right axilla. CONCLUSION: Preliminary studies of a potential new dye for sentinel lymph node identification are presented. It may be the change of the current use of the blue dyes and their severe side-effects on patients submitted to sentinel lymph node biopsies.

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Sentinel lymph node scintigraphy in cutaneous melanoma using a planar calibration phantom filled with Tc-99m pertechnetate solution for body contouring

Medicine and Pharmacy Reports ◽

10.15386/cjmed-637 ◽

2016 ◽

Vol 89 (4) ◽

pp. 480-485

Author(s):

Claudiu Peştean ◽

Elena Bărbuş ◽

Andra Piciu ◽

Maria Iulia Larg ◽

Alexandrina Sabo ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Gamma Probe ◽

Body Contouring ◽

Sentinel Lymph Nodes ◽

Inguinal Region ◽

Dose Rates ◽

Planar Calibration ◽

Flood Source

Background and aims. Melanoma is a disease that has an increasing incidence worldwide. Sentinel lymph node scintigraphy is a diagnostic tool that offers important information regarding the localization of the sentinel lymph nodes offering important input data to establish a pertinent and personalized therapeutic strategy. The golden standard in body contouring for sentinel lymph node scintigraphy is to use a planar flood source of Cobalt-57 (Co-57) placed behind the patients, against the gamma camera. The purpose of the study was to determine the performance of the procedure using a flood calibration planar phantom filled with aqueous solution of Technetion-99m (Tc-99m) in comparison with the published data in literature where the gold standard was used.Methods. The study was conducted in the Department of Nuclear Medicine of Oncology Institute “Prof. Dr. Ion Chiricuţă” Cluj-Napoca in 95 patients, 31 males and 64 females. The localization of the lesions was grouped by anatomical regions as follows: 23 on lower limbs, 17 on upper limbs, 45 on thorax and 10 on abdomen. The calibration flood phantom containing aqueous solution of Tc-99m pertechnetate was used as planar source to visualize the body contour of the patients for a proper anatomic localization of detected sentinel lymph nodes. The radiopharmaceutical uptake in sentinel lymph nodes has been recorded in serial images following peritumoral injection of 1 ml solution of Tc-99m albumin nanocolloids with an activity of 1 mCi (37 MBq). The used protocol consisted in early acquired planar images within 15 minutes post-injection and delayed images at 2-3 hours and when necessary, additional images at 6-7 hours. The acquisition matrix used was 128x128 pixels for an acquisition time of 5 - 7 minutes. The skin projection of the sentinel lymph nodes was marked on the skin and surgical removal of detected sentinel lymph nodes was performed the next day using a gamma probe for detection and measurements.Results. The sentinel lymph nodes were detected in 92 cases and confirmed with the gamma probe during the surgical procedure. The localization of the lymph nodes was as follows: for the tumors localized on lower limb 23 lymph nodes were localized in inguinal region, for the tumors localized on upper limb, 17 lymph nodes were localized in axilla, for the tumors localized on the thorax, 40 lymph nodes were localized in axilla and 3 were localized in the inguinal region; for the tumors localized on the abdomen, 1 lymph node was localized in axilla and 8 lymph nodes was localized in inguinal region. Regarding the negative sentinel lymph node cases, 2 cases were registered for primarily lesions localized on thorax and 1 for a lesion localized on abdomen. According to histology, 26 cases revealed lymphatic metastatic invasion. Dose rates measured at 1m from the calibrator phantom had an average value of 3.46 μSv/h (SD 0.19) and at 1.4m, the value was 2.57 μSv/h (SD 0.22). Dose rates measured at the same distances from the Co-57 planar flood source had a average values of 32.5μSv/h (SD 0.11) respectively 24.1 μSv/h (SD 0.14).Conclusion. The planar calibration flood phantom is an effective tool for body contouring in sentinel lymph node scintigraphy and offers accurate anatomical information to efficiently localize the detected sentinel lymph nodes in melanoma, being for the first time used and mentioned as a pertinent alternative in our department.

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ICG/NIR TECHNIQUE IN LYMPH NODE MAPPING IN PATIENTS WITH COLORECTAL CANCER

Art of Medicine ◽

10.21802/artm.2021.2.18.97. ◽

2021 ◽

pp. 97-102

Author(s):

S. V. Maliborska ◽

V. V. Holotiuk ◽

Y. D. Partykevych

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Indocyanine Green ◽

Treatment Strategy ◽

Near Infrared ◽

Sentinel Lymph Nodes ◽

Optimal Treatment Strategy

Most cancers in humans are epithelial in nature and such neoplasms metastasize via lymphatics; therefore, the lymphatic system plays a pivotal role in a significant number of malignancies. The hematologic behavior of metastatic cancer has been extensively studied, but little is known regarding lymphatic metastasis. Sentinel lymph node (SLN) is the first node to receive the drainage directly from a tumor. Detection and pathological examination of the SLN is an important oncological procedure that minimizes morbidity related to extensive nodal dissection. After many years of observation and research on its use in various malignancies SLN biopsy has become the standard surgical treatment in patients with malignant melanoma, breast and cervical cancers. Today, the issue of diagnosing lymphogenous metastasis in patients with colorectal cancer remains relevant. Standardized methods for examining lymph nodes do not allow to reliably establish the presence of their metastatic lesions. For a more effective assessment, additional examinations are carried out to identify the sentinel lymph node and its precision study, in particular, one of the newest methods is mapping of sentinel lymph nodes using Indocyanine Green (ICG) using near infrared radiation (NIR). Along with the introduction of new technologies, such as the fluorescent dyes indocyanine green (ICG) and near-infrared fluorescence (NIR), and pathologic ultrastaging, Indocyanine green fluorescence-imaging (ICG-FI) has emerged as a potential tool for increasing the accuracy of staging of patients with primary colorectal cancer (CRC) through the detection of sentinel lymph nodes (SLNs). Indocyanine green (ICG) is an inexpensive and safe non-specific fluorescent probe. SLN detection rate has increased and false-negative rate has decreased.Colorectal cancer is the third most common cancer in the Western hemisphere and the incidence increases with increasing age. Surgery is the only curative therapy for localized colorectal cancer and adjuvant chemotherapy is usually recommended for patients with lymph node metastases. Surgery, radiation therapy and chemotherapy are the key components of rectal cancer therapy. Local recurrence greatly affects the treatment efficiency and the survival outcomes for patients with rectal cancer. Lateral pelvic lymph node (LPLN) metastasis (LPNM) is an important factor for local recurrence. Accurate staging TNM of colorectal cancer is essential for evaluating the prognosis and developing an optimal treatment strategy. The presence of metastatic lateral pelvic lymph nodes has been shown to portend a worse prognosis for patients with low rectal cancer. SLN biopsy should be used in this patients for evaluating the prognosis and developing an optimal treatment strategy. Only with all of the above diagnostic tools can accurate diagnosis according to TNM and the choice of the right treatment strategy. The article analyzes and summarizes the scientific literature data on the methods for determining the sentinel lymph node. The sensitivity and specificity of the sentinel lymph node detection using ICG/NIR has been demonstrated. The analysis of various techniques for introducing indocyanine green, the rate of SLN identification was carried out.

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