Lymphatic Mapping Research Articles

Failure of scintigraphy lymphatic mapping in endometrial cancer. Causes and solutions

AimTo evaluate the effect of technical problems and patient characteristics on sentinel lymph node (SLN) scintigraphic detection and mapping success in early stages of endometrial cancer (EC). MethodsPatients with clinical early stage EC (IA-IB) underwent SLN mapping using technetium-99m-nanocolloid, between September 2011 and February 2020 were included. There were excluded cases with technical problems, 92 patients were included for the analysis of the diagnostic performance and the relation of mapping failure (pelvic unilateral or not detected SLN) with patient (age, body mass index, previous pelvic disease or surgery) and disease characteristics (histology, grade, myometrial invasion, lymphovascular space infiltration, tumor size, and lymphatic infiltration risk). ResultsThe overall detection rate was 79%. Lymph node metastases were diagnosed in 7 patients. Age (P = .01), depth of myometrial invasion ≥50% (P = .04) and high risk of lymphatic infiltration (P = .02) were positively associated with mapping failure. In multivariate analysis, age was significantly associated with mapping failure [odds ratio = 1.63, 95%CI: 1.06–2.50; P = .027]. ConclusionsAge, depth of myometrial invasion and high risk of lymphatic infiltration were the factors associated with higher mapping failure.An individualized injection technique, optimizing the methodology, could minimize the detection failures.

Lymphatic Drainage Mapping with Indirect Lymphography for Canine Mammary Tumors.

Simple SummaryMammary gland tumours are the most common canine neoplasms. They account for 25–50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. As mammary gland tumors mainly spread by lymphatic vessels invasion, conceptually, distant metastasis should not be present if the SLN does not have evidence of a tumor burden. In the present study, an indirect lymphography was used for sentinel lymph node mapping in a cohort of 14 adult female dogs with 24 mammary tumors involving the third to the fifth mammary gland. Contrast was injected around the mammary tumor, and lymph nodes that picked up the contrast were visible after 24 h. The results of this study indicate that the lymph drainage pattern of the neoplastic mammary gland may be different for each tumor. The knowledge of the SLN of the neoplastic mammary glands should be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis.Mammary gland tumors are the most common canine neoplasms. They account for 25–50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. The aim of this study is to investigate the SLN with indirect lymphography for a mammary tumor in dogs. The knowledge of the precise drainage pattern and SLN of the neoplastic mammary glands would provide clinically relevant information to the surgeon and to the oncologist, and it would be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis.

Sentinel lymph node in vulvar cancer.

Lymph node removal as a part of surgical management is a standard of care in vulvar cancer patients. Due to patient morbidities and difficulties in treatment of inguinal healing after lymph nodes removal, lymphatic mapping has emerged as an increasingly popular option over the past few years. At this time several different techniques have been described and variety of different dyes were used. In addition, an important aspect of the use of the sentinel lymph node (SLN) technique is the removal of a limited number of lymph nodes, which allows more detailed pathological examination. Moreover, the interpretation of pathological ultra-staging of SLNs, which can identify low-volume metastases for which the clinical significance and the ideal management, remain uncertain. Despite differences in techniques and dyes used, this minimally invasive procedure is currently recommended as an alternative to full inguinofemoral lymph node dissection in selected cases by all major international societies. As for now SLN concept became a standard of care in vulvar cancer. This technique, though simple as a concept, requires a learning curve and should only be used in expert centers. This article provides a review on literature on SLN technique in vulvar cancer, current recommendations and future lines of investigation.

ICG Lymphography in a 4-week Postmortem Cadaver: Implications for a Supermicrosurgery Training Model

Summary:Surgical models are invaluable resources for training and for research and innovation. In the field of supermicrosurgery (SM), options for surgical models remain limited and imperfect. We report the use of a fresh, previously frozen 4-week postmortem cadaveric specimen for successful distal to proximal indocyanine green (ICG) lymphography of the upper extremity. Our technique was confirmed with handheld SPY fluorescence imaging, which visualized a clearly defined, linear lymphatic system. By outlining a straightforward, reproducible method of lymphatic mapping in cadaveric specimens, our group aims to expand the frontiers of surgical models for SM.

Use of Ultrasmall Core-Shell Fluorescent Silica Nanoparticles for Image-Guided Sentinel Lymph Node Biopsy in Head and Neck Melanoma

Sentinel lymph node (SLN) mapping agents approved for current surgical practice lack sufficient brightness and target specificity for high-contrast, sensitive nodal visualization. To evaluate whether an ultrasmall, molecularly targeted core-shell silica nanoparticle (Cornell prime dots) can safely and reliably identify optically avid SLNs in head and neck melanoma during fluorescence-guided biopsy. This nonrandomized clinical trial enrolled patients aged 18 years or older with histologically confirmed melanoma in whom SLN mapping was indicated. Exclusion criteria included known pregnancy, breast-feeding, or medical illness unrelated to the tumor. The trial was conducted between February 2015 and March 2018 at Memorial Sloan Kettering Cancer Center, with postoperative follow-up of 2 years. Data analysis was conducted from February 2015 to March 2018. Patients received standard-of-care technetium Tc 99m sulfur colloid followed by a microdose administration of integrin-targeting, dye-encapsulated nanoparticles, surface modified with polyethylene glycol chains and cyclic arginine-glycine-aspartic acid-tyrosine peptides (cRGDY-PEG-Cy5.5-nanoparticles) intradermally. The primary end points were safety, procedural feasibility, lowest particle dose and volume for maximizing nodal fluorescence signal, and proportion of nodes identified by technetium Tc 99m sulfur colloid that were optically visualized by cRGDY-PEG-Cy5.5-nanoparticles. Secondary end points included proportion of patients in whom the surgical approach or extent of dissection was altered because of nodal visualization. Of 24 consecutive patients enrolled (median [interquartile range] age, 64 [51-71] years), 18 (75%) were men. In 24 surgical procedures, 40 SLNs were excised. Preoperative localization of SLNs with technetium Tc 99m sulfur colloid was followed by particle dose-escalation studies, yielding optimized doses and volumes of 2 nmol and 0.4 mL, respectively, and maximum SLN signal-to-background ratios of 40. No adverse events were observed. The concordance rate of evaluable SLNs by technetium Tc 99m sulfur colloid and cRGDY-PEG-Cy5.5-nanoparticles was 90% (95% CI, 74%-98%), 5 of which were metastatic. Ultrabright nanoparticle fluorescence enabled high-sensitivity SLN visualization (including difficult-to-access anatomic sites), deep tissue imaging, and, in some instances, detection through intact skin, thereby facilitating intraoperative identification without extensive dissection of adjacent normal tissue or nerves. This study found that nanoparticle-based fluorescence-guided SLN biopsy in head and neck melanoma was feasible and safe. This technology holds promise for improving lymphatic mapping and SLN biopsy procedures, while potentially mitigating procedural risks. This study serves as a first step toward developing new multimodal approaches for perioperative care. ClinicalTrials.gov Identifier: NCT02106598.

Assessment of the Completeness of Lymph Node Dissection Using Indocyanine Green in Laparoscopic and Robotic Gastrectomy for Gastric Cancer – A Review

More recently, few scientists have attempted to figure out how to improve the careful recognizable proof of the lymphatic waste courses and lymph node stations during radical gastrectomy in this way beginning another examination outskirt in this field called surgery. Among the distinctive detailed arrangements, the presentation of the indocyanine green has drawn consideration for its attributes, a fluorescence colour that can be identified in the near-infrared spectral band. A fluorescence imaging innovation has been coordinated with frameworks of lymph node dissection in laparoscopic and robotic gastrectomy surgery for gastric cancer. Current confirmations uncover that ongoing vessel navigation by using indocyanine green fluorescence during laparoscopic gastrectomy was demonstrated doable with negligible complications. Its utilization may empower the presentation of fruitful robotic or laparoscopic pylorus-preserving gastrectomy with a decrease in unintended intraoperative wounds, for example, second rate polar dead tissue of the spleen during laparoscopic gastrectomy. The clinical ramifications of utilization of indocyanine green in laparoscopic and robotic gastrectomy for gastric cancer was, in any event, for surgeons with a significant level of involvement with laparoscopic D2 dissection, the near-infrared imaging framework can fill in as a complimentary apparatus to affirm total lymphatic node dissection in patients with atypical life structures. With some restrictions the incorporated innovation of indocyanine green fluorescence with near-infrared imaging systems was practical and a promising strategy for lymphatic mapping in laparoscopic and robotic gastrectomy for gastric cancer.

La peur bleue de ne pas retrouver le bon bleu

In medicine, blue dyes are widely used for lymphatic mapping and biopsy of sentinel lymph nodes in patients with malignant tumors. Three dyes are used for this purpose, namely patent blue, isosulfan blue and methylene blue. They are also used to stain tissues for chromoendoscopy. Reports of anaphylactic reactions to blue dyes are increasing. The allergological work-up is based mainly on history. In the case of perioperative anaphylaxis, it relies on a thouroughly review of the perioperative record. The incorrect identification of the blue dye in the peroperative record will lead to an incorrect diagnosis which could cause serious consequences for patients in case of re-exposure. We describe here two cases of patients who presented peroperative anaphylactic shocks. Both of them had the wrong dye identified in their perioperative record.

Robotic Proximal Gastrectomy with Double-Tract Reconstruction for Gastroesophageal Junction Cancer

The current standard surgical procedure for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal involvement is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to decreased levels of ghrelin (a “hunger hormone” secreted by the stomach) and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) with an anti-reflux technique such as double-tract reconstruction (DTR) can improve quality of life (QoL) by preserving gastric function.1 A recent Japanese prospective GEJ adenocarcinoma study reported a low incidence of lymph node metastases at peripyloric stations,2 indicating the oncological safety of PG for GEJ adenocarcinoma regardless of tumor stage. As a result, PG is increasingly performed in South Korea and Japan, although the QoL benefit of PG over TG remains unknown.3, 4 We have performed PG with DTR in select cases with satisfying short-term outcomes. In this video, we introduce our technique for robotic PG with DTR. The presented case is a 75-year-old woman with GEJ adenocarcinoma that showed an excellent response to preoperative chemoradiation therapy. The patient underwent robotic PG with DTR. Fluorescent sentinel lymphatic mapping was performed by injecting indocyanine green solution (total of 2 ml, at four quadrants around the tumor at submucosal space) via endoscopy at the beginning of the operation. It showed absence of sentinel lymphatic flow to peripyloric lymph nodes, which were thus considered safe to preserve. Pathologic examination confirmed a complete response. The patient’s recovery was favorable, and she reported satisfaction with her QoL and good appetite, though some intermittent bloating after eating. PG with DTR has theoretical disadvantages including incomplete lymph node removal, which may result in recurrence; therefore, PG should be carefully performed for P/GEJ cancers with low risk of perigastric lymph node metastases, such as cT1 tumors or GEJ tumors with limited gastric involvement.2 In addition, delayed gastric emptying of the remnant stomach can cause upper gastrointestinal symptoms such as reflux and bloating. The QoL benefits of PG with DTR must be demonstrated before encouraging its use in the USA and other countries. International collaboration is warranted to test the benefits and safety of PG, and the effective use of sentinel lymphatic mapping, to standardize the surgical care of patients with P/GEJ cancers.

A single-center, self-controlled, phase I clinical trial of mitoxantrone hydrochloride injection for lymph tracing for sentinel lymph node identification of breast cancer.

Mitoxantrone hydrochloride injection for lymph tracing (MHI) is a novel lymphatic tracer for sentinel lymph node (SLN) in patients with early breast cancer but exhibited remarkable liver, kidney, and hematologic toxicities in previous studies. Here, the pharmacokinetics and pharmacodynamics profiles of MHI were evaluated to surmise safety and tolerability. Phase 1 open-label, single center, and dose escalation study was performed. Ten patients with invasive breast cancer received 0.5, 1.0, or 2.0 mL of MHI into the breast tissues surrounding the tumor for lymphatic mapping. All of these patients were injected with 2 mCi nuclide-labeled sulfur colloid as a self-control 24 to 48 hours before surgery. Safety was assessed by the incidence of adverse events graded by the National Cancer Institute Common Terminology Criteria, version 4.0.3 (CTCAE4.0.3). Blood samples for pharmacokinetic analyses were collected before and after administration at 15, 30, 60, 120, and 240 min of the injection of MHI. Up to the cutoff date of the study (Aug 8, 2018), no dose-limiting toxic effects or obvious allergic reactions were observed. Only one case of an adverse event was certainly related to MHI, where it caused blue discoloration of the local skin over the injection site after the operation, but this stain gradually went away. The peak level of MHI was achieved after 15-30 min post injection and completely eliminated from the plasma after 60 min. There were no significant differences in the number of lymph nodes detected by MHI and radioactive colloid. Only one patient with lymph node macrometastases had no SLN detected by either the radioactive colloid or the MHI. At a dose of up to 2.0 mL, MHI was well tolerated and safe for conducting SLN biopsies in patients with breast cancer. Although there was a case with blue discoloration of the local skin over the injection site after the operation, and remained for a short period of time, but the overall safety was acceptable. Here, we approached a novel SLN tracing slant; however, more investigations of MHI should be performed for further evaluations. (Chinadrugtrials.org.cn number: CXHL1301201, Date of registration: October 12, 2015.).

Abstract PS1-62: Two decades of experience with sentinel node staging of axilla - is false negative no longer a worry?

Abstract Aim: To review current literature and standard practices in various techniques of sentinel node biopsy for staging the axilla for treating early breast cancer. The purpose is to provide evidence based recommendation as guidance platform for optimal true sentinel node retrieval irrespective of surgeon expertise. Background: Axillary conservation is the way forward after game changing trials like ACOSOG Z0011, surrogate trials like IBCSG,AMAROS, ALMANAC, ongoing POSNOC, and newbie ATNEC have progressively or plan to decrease the need to unnecessarily fiddle with the axilla thereby increasing the chances of arm related and other morbidities. Axillary sentinel node biopsy entails retrieval of first draining lymph node in the breast-axilla pathway to plan treatment in breast cancer by appropriate staging of axilla. Current standard is the utilisation of double agent technique with radioactive isotope and blue dye injection to decrease false negative rates for true sentinel node retrieval. Novel techniques like magnetic and infrared tracing are still being investigated for validation. Method: PMC, Medline, EMBASE, PubMed and Cochrane library searched for clinical trials, randomised trials, systematic reviews and meta-analysis on techniques of axillary sentinel node biopsy in early breast cancer. This covered the last 25 years literature on the topic. Results: The search yielded 197 publications which were subjected to a meticulous review and narrowed to a select pertinent body of evidence to extrapolate suggested guidance rationally, the bibliography of which is provided at the end. Conclusion: Single agent preferably radioisotope for lymphatic mapping is recommended in palpable and good biology tumours. Use of single agent blue dye can be standardised in axillary tail tumours. It is also recommended as being effective when isotope mapping is logistically not feasible or during pandemics like COVID 19 where looming infrastructure challenges are prevalent. Dual agent technique should be considered in previously treated breast and axilla, neoadjuvant chemotherapy cohort, bad tumour biology, high BMI and macromastia groups for true nodal retrieval. Optimal number of nodes taken out should not be more than three (n=3). Lower axillary sampling of not more than 3 nodes is recommended for troubleshooting with any localising agent technique. Triple site injection at peri-tumoural, subcutaneous and sub areolar regions and larger volume of blue dye agent injection of up to 8mls increases the localisation success in the dual technique group for lymphatic mapping. Magnetic tracing can be used as an adjunct to either single agent radioactive isotope or blue dye (RI/BD) technique when there is failure to localise the sentinel node. Citation Format: Tahera Arif, Mohammed Shamim Absar. Two decades of experience with sentinel node staging of axilla - is false negative no longer a worry? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-62.

Post-operative follow-up of 150 patients with sentinel lymph node biopsy under tumescence local anesthesia.

Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. 32% of the patients reported post-operative pain within the first 48h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3% of the patients. 98.7% of the patients were satisfied with SLNB under TLA. SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

Pb-Doped Ag2 Se Quantum Dots with Enhanced Photoluminescence in the NIR-II Window.

Ag2 Se quantum dots (QDs) as an effective biological probe in the second near-infrared window (NIR-II, 1000-1700nm) have been widely applied in bioimaging with high tissue penetration depth and high spatiotemporal resolution. However, the ions deficiency and crystal defects caused by the high Ag+ mobility in Ag2 Se crystals are mainly responsible for the inefficient photoluminescence (PL) of Ag2 Se QDs. Herein, a tailored route is reported to achieve controllable doping of Ag2 Se QDs in which Ag is exchanged by Pb via cation exchange (CE), which is unattainable by direct synthetic methods. The Pb-doped Ag2 Se QDs (denoted as Pb:Ag2 Se QDs) present fire-new optical features with significantly enhanced PL intensity of 4.2 folds. Photoelectron spectroscopy confirms that Pb acts as an n-type dopant for Ag2 Se QDs and therefore the electronic impurities provide additional carriers to fill the traps. Moreover, the general validity of this method is demonstrated to convert different sized Ag2 Se into Pb:Ag2 Se QDs, so that a wide range of NIR-II PL with high intensity is obtained. The bright NIR-II emission of Pb:Ag2 Se QDs is further successfully performed in lymphatic system mapping.

Performance of Indocyanine-Green Imaging for Sentinel Lymph Node Mapping and Lymph Node Metastasis in Esophageal Cancer: Systematic Review and Meta-Analysis.

Lymphatic mapping with indocyanine-green (ICG) and near-infrared light fluorescent imaging is widely used for sentinel lymph node staging in different types of cancer but is not fully accepted for all procedures because studies have reported heterogeneous results. This study aimed to assess the detection rate (DR) of ICG imaging for sentinel lymph node mapping (SLNM) and lymph node metastases (LNMs) in esophageal cancer. A systematic search was performed to identify relevant studies examining the use of ICG imaging for SLNM in patients with esophageal cancer. Extracted results were pooled in a single-proportion meta-analysis, with a random-effects model, presented as forest plots. Six studies were included in the analysis. The ICG DR for SLNM was 89% [95% confidence interval (CI) 71%-96%]. The pooled sensitivity and specificity values for the detection of LNMs were 84% (95% CI 64%-94%) and 15% (95% CI 3%-45%), respectively. A trend towards a lower DR was found with increasing mean latency time between ICG injection and SLNM. ICG imaging is a technique that potentially could improve lymph node yield excision and, as a consequence, improve the detection of lymph node metastases.

Interventional nuclear medicine: a focus on radioguided intervention and surgery.

Within interventional nuclear medicine (iNM) a prominent role is allocated for the sub-discipline of radioguided surgery. Unique for this discipline is the fact that an increasing number of clinical indications (e.g. lymphatic mapping, local tumor demarcation and/or tumor receptor targeted applications) have been adopted into routine care. The clinical integration is further strengthened by technical innovations in chemistry and engineering that enhance the translational potential of radioguided procedures in iNM. Together, these features not only ensure ongoing expansion of iNM but also warrant a lasting clinical impact for the sub-discipline of radioguided surgery.

SURGICAL TREATMENT FOR BREAST CANCER AND AXILLARY METASTASES: HISTORICAL PERSPECTIVE

Breast cancer (BC) is the most common malignancy to affect females. The first suggestions of BC and its treatment date back to Ancient Egypt, 1500-1600 B.C. Throughout history, the management of BC has evolved from extensive radical mastectomy towards less invasive treatments. Radical mastectomy was introduced by W.S. Halsted in 1894, involving the resection of the breast, regional lymph nodes, pectoralis major and minor. Despite its mutilating effect, it had been the main surgical approach to BC patients until 1948, when Patey and Dyson proposed its modified form that conserved pectoralis major and minor and the level III of axillary lymph nodes. The latter was associated with less postoperative morbidity and improved quality of life. The idea of limited breast tissue resection was introduced in the 1970s by Umberto Veronesi and led to further minimizations of surgery in BC patients until breast conservation became the standard of care for early-stage disease. In the 1990s, intraoperative lymphatic mapping and the concept of sentinel lymph node (SLN) biopsy (SLNB) have been developed. SLNB has replaced axillary lymph node dissection (ALND) to be the standard procedure for axillary staging in patients with clinically node-negative BC. Many women have since been spared ALND, including those with negative SLNB or with SLNs involved with micrometastases (0.2-2 mm in size). In the last decade, evidence gathered from new clinical trials suggests that ALND may be safely omitted even in BC patients with 1 or 2 positive SLNs if adjuvant radiotherapy is delivered.

Aberrant Lymphatic Drainage of Primary Invasive Lobular Carcinoma with Concurrent Primary Lung Adenocarcinoma: A Case Report

Background: Lymphatic spread of breast cancer is currently well understood and can be assessed in breast cancer patients through the use of lymphatic mapping with sentinel node biopsy, CT, PET.
 The Case: Here we present a case report of a 73-year-old female with two distinct primary carcinomas, right-sided invasive lobular carcinoma of the breast and left-sided adenocarcinoma of the lung. We also discuss the predictable and unpredictable lymphatic drainage of the lobular carcinoma, including ipsilateral drainage to the axillary chain and suspected contralateral hilar and mediastinal lymph node metastasis.
 Conclusion: The unique lymphatic spread of breast cancer, in this case, emphasizes the use of lymphatic mapping for the staging of disease and staining biopsied tissue samples for tumor markers to guide treatment. Additional anatomic research in this patient or supporting reported cases are needed to determine the frequency and cause of aberrant lymphatic drainage of primary invasive lobular carcinoma of the breast.

Anatomy and physiology of the sentinel lymph nodes of the upper extremity: Implications for axillary reverse mapping in breast cancer.

This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

Novel Experience in Hybrid Tracers: Clinical Evaluation of Feasibility and Efficacy in Using ICG-99mTc Nanotop for Sentinel Node Procedure in Breast Cancer Patients.

The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed. The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.

Does 99mTc-tilmanocept, as next generation radiotracer, meet with the requirements for improved sentinel node imaging?

Introduction and objectivesTo evaluate the migration of 99mTc-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients with breast cancer and melanoma, scheduled for SN biopsy after interstitial tracer administration. Materials and methodsFor 29 primary tumours in 28 patients (mean age: 62y, range: 45–81y) scheduled for SN biopsy planar images were acquired 10 and 120min after administration of 74MBq 99mTc-tilmanocept, in order to evaluate lymphatic drainage as well as uptake ratios between injection site (IS), SN and non-SN. SPECT-CT was performed immediately after delayed planar images to enable anatomical lymph node localization. ResultsSNs were visualized in all patients (100%) with drainage to 34 basins. Uptake in non-SNs was perceived in 16 basins (47%). Number of SNs was concordant between early and delayed images in all basins excepting five (86%). In 24 patients tracer migrated to one lymph node basin (LNB), in three to 2 and in one to 4. When IS was included (N=29) on image, IS/SN ratio could be measured per LNB. The IS/SN ratio at 2h compared to 15min decreased with an average of 66% (range: 15–96%). SN/non-SN 2h ratio in LNBs with visible non-SNs averaged 6.6 (range: 2.3–15.6). In 9 patients with two SNs SN1/SN2 ratio averaged 1.9 on delayed images. At histopathology, SNs were found to be tumour positive in 7 basins (20%). Conclusion99mTc-tilmanocept appears to meet the requirements for improved SN imaging in breast cancer and melanoma on the basis of early and persistent SN visualization frequently accompanied by no or markedly less non-SN uptake. This is associated to rapid migration from the injection site together with increasing SN uptake and retention as expressed by decreasing IS/SN and persistently high SN/non-SN ratios. Further head-to-head comparison of 99mTc-tilmanocept with standard SN radiotracers in larger series of patients is necessary.

Utility of Intraoperative Fluorescence Imaging in Gynecologic Surgery: Systematic Review and Consensus Statement.

This study aimed to review the current knowledge on the utility of intraoperative fluorescence imaging in gynecologic surgery and to give evidence-based recommendations to improve the quality of care for women who undergo gynecologic surgery. A computer-based systematic review of the MEDLINE, CENTRAL, Pubmed, EMBASE, and SciSearch databases as well as institutional guidelines was performed. The time limit was set at 2000-2019. For the literature search, PRISMA guidelines were followed. A modified-Delphi method was performed in three rounds by a panel of experts to reach a consensus of conclusions and recommendations. Indocyanine green (ICG) is used primarily in gynecology for sentinel node-mapping. In endometrial and cervical cancer, ICG is a feasible, safe, time-efficient, and reliable method for lymphatic mapping, with better bilateral detection rates. Experience in vulvar cancer is more limited, with ICG used together with Tc-99m as a dual tracer and alone in video endoscopic inguinal lymphadenectomy. In early ovarian cancer, results are still preliminary but promising. Indocyanine green fluorescence imaging also is used for ureteral assessment, allowing intraoperative ureteral visualization, to reduce the risk of ureteral injury during gynecologic surgery. For most gynecologic cancers, ICG fluorescence imaging is considered the tracer of choice for lymphatic mapping. The use of this new technology expands to a better ureteral assessment.