Isosulfan Blue Dye Research Articles

New concept in selecting blue dye injection site effect on clinical outcome of early-stage breast cancer patients: a retrospective cohort

BackgroundClinico-anatomical review and pilot studies demonstrated that intraparenchymal injection at any site, even those not containing the index lesion, or periareolar injections should provide concordant outcomes to peritumoral injections.MethodThis was a single-center retrospective cohort at King Chulalongkorn Memorial Hospital. The electronic medical records of patients were characterized into conventional and new injection concept groups. The inclusion criteria were patients who had either a mastectomy or BCS along with SLNB. We excluded patients who underwent ALND, received neoadjuvant therapy, or had non-invasive breast cancer. The primary outcome was the 5-year rate of breast cancer regional recurrence. Additionally, we reported on the re-operation rate, disease-free period, distant disease-free period, mortality rate, and recurrence rates both locoregional and systemic. Recurrences were identified through clinical assessments and imaging. Surgical technique: 3 ml of 1%isosulfan blue dye was injected, with the injection site varying according to the specific concept being applied. In cases of SSM and NSM following the new concept, the blue dye was injected at non-periareolar and non-peritumoral sites. After the injection, a 10-minute interval was observed without massaging the injection site. Following this interval, an incision was made to access the SLNs, which were subsequently identified, excised, and sent for either frozen section analysis or permanent section examination.ResultThere were no significant differences in DFS, DDFS or BCSS between the two groups (p = 0.832, 0.712, 0.157). Although the re-operation rate in the NI group was approximately half that of the CI group, this difference was not statistically significant (p = 0.355).ConclusionOur study suggests that tailoring isosulfan blue dye injection site based on operation type rather than tumor location is safe and effective approach for SLN localization in early-stage breast cancer. However, this study has limitations, including being a single-center study with low recurrence and death cases. Future studies should aim to increase the sample size and follow-up period.

Case Report: Isosulfan Blue-Related Anaphylaxis.

Anaphylaxis is an acute multisystem syndrome typically resulting from the sudden release of mast cell and basophil-derived mediators into the circulatory system. Isosulfan blue dye is a rare, but known, mediator of anaphylaxis with an incidence between 0.16% and 2% of cases. We report two cases of anaphylaxis attributed to the use of isosulfan blue dye in the intraoperative setting. Both of the patients we report had grade 3 anaphylactic reactions requiring vasopressors to correct significant hypotension. Both patients required overnight monitoring in the intensive care unit with the second patient also requiring continued vasopressor support.

Abstract P1-01-02: Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping

Abstract Background Breast cancer is the most common cancer in female patients worldwide. Although axillary management in breast cancer has been de-escalated to reduce untoward effects, breast cancer-related lymphedema (BCRL) is still not uncommon. Axillary reverse mapping (ARM) emerges as a novel technique that identifies the lymphatic system draining the upper extremities. Preservation of this system and associated lymph nodes theoretically reduces the chance of BCRL. However, concerns regarding oncologic safety have limited the adoption of the technique. Objective To identify factors associated with metastatic disease in lymph nodes identified by ARM in breast cancer patients. Materials and methods Breast cancer patients treated at King Chulalongkorn Memorial Hospital from October 2018 to January 2021 who underwent axillary lymph node dissection (ALND) underwent concurrent ARM whereby five milliliters of 1% isosulfan blue dye was injected at the medial aspect of the arm as previously described elsewhere. Patient demographics and clinical data such as clinical staging, pathological staging, cancer subtype, and whether neoadjuvant chemotherapy was administered were collected and analyzed. Result Thirty-six patients with a median age of 57 were included in this prospective study. ARM lymph node identification success rate was 83% (30 of 36 patients) with a median of 2 identified ARM lymph nodes (range 0-11 nodes). Metastatic disease in ARM nodes was present in 30% of patients. ARM success rate did not depend on whether preoperative chemotherapy had been given (ARM lymph nodes identified in 7 out of 8 patients without preoperative chemotherapy and 23 out of 28 in patients with preoperative chemotherapy; p=0.36). There was no statistically significant difference in metastatic disease in ARM-identified nodes and clinical stage (stage II=13.3%, stage III=33.3%, and stage IV=50.0%; p=0.18). However, higher pathologic N stage was associated with finding metastasis in ARM-identified lymph nodes (N0=0%, N1=15.8%, N2=33.3%, and N3=80%; p=0.005). Conclusions ARM is a novel technique which can potentially reduce BCRL. However, a significant number of ARM lymph nodes were found to have pathologically-proven metastatic disease, especially in higher pathologic N stages (pN2 and pN3). Therefore, for oncologic safety, consideration should be given to removal of all ARM lymph nodes in breast cancer patients undergoing formal axillary dissection. Keywords: Axillary Reverse Mapping, Axillar dissection, Lymphedema, Breast Cancer Citation Format: Rak Saengphongchawan, Sopark Manasnayakorn. Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-02.

Feasibility of Magnetic Technique for Axillary Staging after Neoadjuvant Therapy in Breast Cancer Patients

Purpose Optimal axillary staging after neoadjuvant chemotherapy (NAC) in node-negative breast cancer is an area of controversy. Sentinel node biopsy with Technetium-sulphur colloid (99m Tc) alone or with blue dye is the recommended technique for evaluating axilla in these patients. However, this technique has drawbacks such as limited access to nuclear departments and timing limitations related to Tc injection exposing patients to unnecessary radiation. Superparamagnetic iron oxide nanoparticles (SPIO) may represent a valid option for SLN biopsy. In this study, we assessed the feasibility of the magnetic technique (Sentimag) with combination of isosulfan blue dye in breast cancer patients who received NAC. Methods The study sample consisted of 54 female breast cancer patients who received NAC. Sentinel node localization was performed using magnetic technique and blue dye. Sentinel node identification rate (IFR) of magnetic technique was calculated and postoperative complications were assessed. Results Sentinel lymph node was detected in 52 patients with Sentimag method (identification rate = 96.3%, 95% CI: 87.4–98.9%). Blue dye was successful to find SLN in 38 patients (identification rate = 70%). The most common histologic type was invasive ductal (n = 51; 94.4%). Mean tumor size was 2.1 cm after NAC. Most of patients had T2 (n = 30; 55.5%) and HER2 + positive (n = 49; 90.7%) cancer. Conclusion Sentimag which is a magnetic technique appears to be safe, easy to perform with minimal adverse effects, may be an alternative and accurate technique in patients with NAC, especially in breast units where nuclear medicine unit is not available. Supplemental data for this article is available online at https://doi.org/10.1080/08941939.2022.2038737 .

653 Adverse Effects of Isosulfan Blue Dye in Sentinel Lymph Node Mapping in Breast Cancer: A meta-analysis

Abstract Aim The aim of the study is to investigate the available evidence on the adverse effects of the use of isosulfan blue dye in sentinel lymph node mapping in breast cancer patients and to determine the treatment modalities for such complications. Method We carried out a thorough search of relevant articles in PubMed, Medline and Embase databases using the PRISMA guideline. Studies reporting on the adverse effects of isosulfan blue dye were included. Adverse effects were subdivided into 3 groups: Grade I, Grade II and Grade III. Weighted means were extracted and evaluated for procedure adverse reactions. A meta-analysis of proportion was conducted using random-effect models to analyse adverse effects rates. Results Grade I reactions were seen in 184 patients, Grade II in 4 patients and 50 patients developed Grade III reactions. The total rate of adverse reactions was 1.10% [CI: 0.96 to 1.26]; Grade I reaction rate was 0.82% [CI: 0.70 to 0.96], Grade II reaction rate was 0.02% [CI: 0.006 to 0.054] and Grade III reaction rate was 0.24% [CI = 0.18 to 0.32]. Conclusions Currently, there is no level 1 evidence (meta-analysis) in the literature on the use of isosulfan blue dye in sentinel lymph node mapping in breast cancer patients. In our study, despite the low adverse reaction rate of isosulfan use, clinicians should still be aware of such complications following administration to ensure prompt treatment.

Reverse Axillary Mapping in Breast Cancer Using Blue Dye: A Tertiary Setup Experience.

The concept of reverse axillary mapping originated with the main purpose of reducing lymphedema. In this study, we test the advantage of reverse axillary mapping to delineate the arm-draining lymph nodes and their involvement in various stages of breast carcinoma. In this study, we also attempt to redefine the template for axillary dissection in breast cancer.During the period of September 30, 2020, to August 30, 2021, 46 patients were recruited to undergo a procedure in which isosulfan blue dye was injected into the upper arm and the axilla was explored to isolate the lymph nodes. The lymph nodes were submitted for examination histopathologically.The results conclusively showed that axillary lymph node metastasis was only influenced by the advanced stage of the disease (p=0.014) and the visualization of the lymphatics was independent of the stage, type of surgery, decubitus, or age.The study conclusively shows that attempts to preserve the upper limb-draining nodes in advanced stages would be futile and the preservation of such lymph nodes should be limited to the early stages of breast cancer.

Precise Intraoperative Lymph Node Identification by Isosulfan Blue of Occult Neck Lymph Node Metastases for Decision to Convert from Supraomohyoid Neck Dissection to Comprehensive Neck Dissection in Early-Stage Oral Cancer

Objective: To study the sensitivity and specificity of peritumoral isosulfan blue dye injection for localization of suspected metastatic lymph nodes.
 Materials and methods: The study included all patients diagnosed with early-stage oral cancer between January 2018 and March 2020. After elevation of the skin flap, the primary site was injected peritumorally with isosulfan blue 0.3-0.5 cc at 1 cm intervals and massaged. The time at which any draining nodes turned blue was recorded and the node was then excised for frozen section. After which supraomohyoid neck dissection was performed. The frozen sections were stained with H&E and analyzed for presence of metastases. Negative sections were further analyzed using immunohistochemistry stains. Sensitivity, specificity and time of identification suspected metastatic lymph node were analyzed .
 Results: Nineteen patients with early-stage oral cancer were included. The majority (78.4%) presented with tongue lesions. The mean injection amount administered was 3.62±0.83 cc, and the number of injections around the tumor were 10.26±2.31. Mean duration from time of injection to the identification of a blue node was 19.26±15.99 min. Nodes at Level I of the neck were the most common identified as blue nodes (57.8%). Statistical analysis comparing pathological findings with blue node identification revealed this technique has a sensitivity of 71.4% with specificity of 91.7% and an overall accuracy of 84.2% in identify metastasis lymph node. 
 Conclusion: Isosulfan blue injection of primary oral tumors demonstrated a high level of efficiency in identifying metastatic lesions in draining lymph nodes. This technique may be helpful in deciding intraoperatively whether to convert from supraomohyoid neck dissection to comprehensive neck dissection .

156P The effectiveness of intraoperative administration of both radioactive isotope and blue dye without pre-surgery gamma imaging in comparison with the conventional technique for sentinel node biopsy

Our departmental audit revealed some problems associated with the conventional technique of SLNB such as scheduling issues for OT, co-ordination issues and time lost in the process. Our analysis showed us that the sentinel node was always in axilla, appeared soon after injection, the injection was painful, and the location of the node did not influence the incision. We sat with our nuclear medicine colleagues and evolved a strategy to overcome these problems: Do away with the imaging under gamma camera; shift injection venue to the operating room, thus avoiding a lot of co-ordination and scheduling issues; avoid pain by injecting isotope after induction of general anaesthesia and; train persons to inject the radioactive material. This study is looking at 200 patients of SLN biopsy done by the conventional technique compared to the next 200 patients done with the dual technique. Intraoperative dual SLN mapping consisted of subareolar injection of technetium 99m- labelled filtered sulphur colloid (15-37 MBq) and 2 ml of 1% iso sulfan blue dye just after anaesthetic induction. The conventional technique consisted of subareolar injection of radioactive colloid in Nuclear medicine followed by SPECT imaging and subareolar injection of blue dye intraoperatively. In both cases the SLN was detected using gamma probe and blue colour. SLN’s identified during these procedures were classified as “blue-hot” nodes, “hot-only” nodes, or “blue-only” nodes. Table: 156PConventional techniqueDual techniqueP valueTotal patients202238Sentinel node detected196 (97%)232 (97.47%)0.773Hot and blue159 (81.12%)204 (87.9%)0.054Hot only36 (18.36%)25 (10.7%)0.027 (significant)Blue only1 (0.51%)3 (1.29%)0.399SLN +VE, Other nodes -VE32240.070Only non SLN +VE620.096SLN +VE, NON SLN +12150.875 Open table in a new tab SLN detection rate of dual technique was equivalent to conventional technique. Thereby, even in the absence of Nuclear medicine facility within the hospital, the SLNB can still be performed by procuring the radioactive colloid from a source at a distant site in the same town or city and using the hand-held gamma probe without affecting sensitivity or detection rates.

Sentinel Lymph Node Biopsy in Early Breast Cancer Using Isosulfan Blue Dye alone in Resource-Limited Centers- Our Experience

Objective To evaluate the efficacy of Sentinel Lymph Node Biopsy in early Breast Cancer using Isosulfan Blue dye alone in areas where nuclear medicine facilities are not available. Material and Methods Data was retrospectively reviewed from July 2019 to December 2020. Only those patients were included who had clinically and radiologically negative axilla without distant metastasis. Those who needed down staging, SLNB was performed after systemic therapy completion. Decision of further axillary dissection in breast conserving surgery (BCS) was based on Z0011 protocol. Patients are followed for locoregional recurrence, disease free survival and overall survival. Results We studied a total of 76 patients, out of which 63 patients underwent BCS (83%) and 13 Patients underwent mastectomy (17%). SLN was successfully identified in all patients except one. Majority of patients were T2 at presentation (82%). Frozen section was negative in 51 patients (71%) and positive in 21 patients (29%). Out of 21 positive SLN, 11 underwent ALND while 10 did not. In 85% of patients total no of LNs removed were 03 or more. Follow-up was short, maximum 2 years and minimum 10 months. One patient showed local recurrence in breast at 6 months after surgery. Rest all were fine, follow-up is still going on. Conclusion Sentinel lymph node biopsy with Isosulfan blue dye alone is an acceptable method in resource-constrained countries, where unfortunately most patients still undergo axillary dissection irrespective of the clinical nodal status. This study may provide an incentive to such countries to adopt this simpler procedure to avoid long-term morbidity of axillary dissection in their patients.

Outcome of Sentinel Lymph Node Biopsy with Methylene Blue Dye in Early-stage Breast Cancer

<i>Background:</i> Axillary staging is the standard of care for all breast cancers amenable to curative treatment. Sentinel lymph node biopsy (SLNB) has been established as the gold standard for axillary staging and has supplanted axillary lymph node dissection (ALND) as a means of regional nodal staging in clinically node-negative breast cancer. Different blue dyes like isosulfan blue dye, patent blue, sulfan blue, radio labeled substances, and methylene blue dye (MBD) have been evaluated for the sentinel node procedure. <i>Aim of the study:</i> The aim of this study was to assess the efficacy of sentinel lymph node biopsy with methylene blue dye in clinically axillary node negative early-stage breast carcinoma as well as to observe the early postoperative outcome of SLN procedure. <i>Method:</i> Between November 2015 to October2017, a total of 18 female patients of 18 years and above, with diagnosis of early-stage (T1/T2) breast carcinoma with clinically negative ipsilateral axillary lymph nodes were studied in the department of surgical oncology, NICRH. Written informed consents were obtained from all patients. <i>Results:</i> In this study, the highest population was in 31-50 years age group with a mean age of 46(SD 12). Out of 18 cases, SLN(s) was identified in 15 cases by using MBD. The identification rate was 83.3%. In frozen section biopsy all SLNs were found positive for malignant cells. Two or more SLNs were positive in 12(66.6%) cases where SLNB was extended to ALND. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100, 50, 80 and 100, respectively. Postoperative morbidity was significantly high in ALND group. <i>Conclusion:</i> This study showed that SLNB is a safe procedure and efficacy of this procedure was very significant. It lowers the unnecessary extended surgery (ALND) which has troublesome postoperative complications. Multicenter studies are required to extract more relevant information in this regard.

An AN OBSERVATIONAL STUDY OF SLN MAPPING IN PATIENTS OF LOCALLY ADVANCED BREAST CANCER FOLLOWING NCT

Background : Locally advanced breast carcinoma (LABC) includes a wide range of clinical scenarios- advanced primary tumors (T4), advanced nodal disease and inflammatory carcinomas(1). Traditionally, treatment of LABC included a combination of Chemotherapy, Radiation and Surgery(2). However, there has been a shift to Neoadjuvant Chemotherapy in recent times.(3)&#x0D; Histological status and the number of axillary lymph nodes with metastasis is one of the most important prognostic factors and most powerful predictor of recurrence and survival in patients of breast carcinoma and remains so, even after neo-adjuvant chemotherapy. (3) Information derived from the sentinel lymph node is considered valuable, with less discomfort to the patient when compared with axillary dissection.(4) However, its role in detecting nodal metastasis after neo-adjuvant chemotherapy in LABC is still debatable and definitive studies to evaluate its role are still evolving. (5)&#x0D; Materials and Methods: Patients of LABC were evaluated using ultrasonography (USG) of axilla. Neo-adjuvant chemotherapy (NACT) was administered and patients were reassessed by USG of axilla. Thirty patients with node negative axillary status were subjected to Sentinel lymph node mapping using isosulfan blue followed by Modified Radical Mastectomy and Axillary Lymph Node Dissection. Histopathological evaluation of stained and unstained lymph nodes done and the data, thus obtained, was statistically analysed.&#x0D; &#x0D; Results: Sentinel lymph node biopsy performed using Isosulfan Blue dye alone, after neo-adjuvant chemotherapy predicts the status of axillary lymph nodes with low accuracy.&#x0D; &#x0D; Conclusions: Further studies would be required to establish the role of sentinel lymph node biopsy in patients with LABC after NACT.

Abstract P4-02-18: Sentinel node biopsy mapping using fluoresceine in breast cancer. An alternative for low and middle income countries

Abstract Background: All methods available for SNB identification suffer from many flaws including cost of the probes, allergies or management of radioactive material. Breast cancer is a challenging issue in LMIC [1]. Fluorescein has been described first in this meeting [2-3] as an alternative cheap and safe tracer in SNB mapping [4]. Our aim was to reproduce the feasibility and the safety of fluorescein SNB mapping compared with Isosulfan blue dye as a reference. Methods: Ten patients, with biopsy proven BC, were operated on for SNB biopsy and prospectively included over a period of one year (April 2018 - April 2019). Patients had 2 cc Isosulfan blue dye and 2 cc 10% fluorescein mixed with 4 cc of 9% saline solution injected subcutaneously in the peri-areolar area prior to lymph node biopsy. Fluorescent lymph nodes were detected by 5 nm ultra-violet light-emitting diode flashlight. They were removed and then remaining blue and/or suspicious nodes were removed. The detection rate and the complications were the primary objectives in this study. Results: Mean age was 40 years old (range 27 - 72). Mean size of the tumor was 20 mm (5 - 70mm). All patients but one had invasive breast carcinoma and one had ductal carcinoma in situ. All patients had no clinical or radiological suspicious nodal involvement before surgery. Six patients had a breast conserving surgery and four had a mastectomy. After a mean delay of 15,5 minutes after injection, SLN sampling was performed. All patients had fluorescent and blue nodes. A total of 27 fluorescent nodes and 25 blue nodes were harvested during these procedures. All blue nodes were fluorescent. Two nodes had micro-metastasis on final pathology. One of them was only detected by fluorescein. Adverse effects were represented by 2 seromas. No patient experienced an allergic reaction. Conclusion: In this pilot study, we were able to reproduce the published data where fluorescein based SNB detection was feasible, efficient in the detection rate and safe. We emphasize the need for a larger multicenter study to confirm the clinical utility of this tracer. The low cost of this technique will greatly help the development of SNB in LMIC Refernces: 1. Bellanger M, Zeinomar N, Tehranifar P, Terry MB. Are Global Breast Cancer Incidence and Mortality Patterns Related to Country-Specific Economic Development and Prevention Strategies? JGO. 8 juin 2018;(4):1-16. 2. Srivastava A, Suresh J, Ranjan P, et al: Fluorescent fluorescein with methylene blue compared to radioactive sulphur colloid with methylene blue: a randomised comparison. Proc SABCS 2017; abstr PD2-03. 3. Srivastava A, Kumar C,Kataria K fluorescence guided breast conserving surgery Proc SABCS 2018 PD 08 06 4. Chang YW, Lee HY, Lee CM, Jung SP, Kim WY, Woo SU, et al. Sentinel lymph node detection using fluorescein and blue light-emitting diodes in patients with breast carcinoma: A single-center prospective study. Asian Journal of Surgery [Internet]. 20 mars 2019. Citation Format: Remy Jacques Salmon, Mehdi Benna. Sentinel node biopsy mapping using fluoresceine in breast cancer. An alternative for low and middle income countries [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-18.

Diffuse skin staining after using isosulfan blue for sentinel lymph node biopsies

A 69-year-old female diagnosed with bilateral invasive lobular breast carcinoma presented to our facility to undergo a bilateral mastectomy with bilateral sentinel lymph node biopsies (SLNB). Pre-operatively, five mL of isosulfan blue dye was injected to the sub-areolar tissue bilaterally and massaged for five minutes just prior to incision. Mild blue staining of the sentinel lymph nodes was noted during the surgery.

Outcomes of "one-day" vs "two-day" injection protocols using Tc-99m tilmanocept for sentinel lymph node biopsy in breast cancer.

No prior studies have compared Tc-99m tilmanocept (TcTM) one-day and two-day injection protocols for sentinel lymph node (SLN) biopsy in breast cancer (BC). We retrospectively identified patients with clinically node-negative BC undergoing SLN biopsy at our institution. Patients received a single, intradermal peritumoral injection of TcTM on day of surgery or day prior to surgery in addition to an intraoperative injection of isosulfan blue dye. Univariable and multivariable Poisson regression count models were constructed to assess the effects of injection timing, radiologist, patient and surgeon characteristics on the number of removed SLNs. A total of 617 patients underwent SLN biopsy with TcTM and blue dye. Sixty-seven (10.9%) patients were injected with the two-day protocol. Patients in the one-day protocol had a mean of 3.0 (standard deviation (SD) 1.9) SLNs removed compared with 2.7 (SD 1.4) SLNs in the two-day protocol, P-value=.13. On multivariable analysis, patient age and operating surgeon significantly affected the number of removed SLNs; however, the injection timing and the nuclear radiologist did not influence the number of removed SLNs. The performance of Tc-99m tilmanocept did not differ significantly between one-day and two-day injection protocols. These results are similar to other radiotracers used for SLN biopsy in BC.

Anaphylactic Reactions to Isosulfan Blue Dye During Sentinel Lymph Node Biopsy for Breast Cancer

Background: The sentinel lymph node biopsy is an alternative to axillary dissection for many breast cancer patients. Cases of anaphylactic reaction to the isosulfan blue dye used during sentinel lymph node biopsy have recently been reported. To prospectively reduce the incidence and severity of adverse reactions to isosulfan blue dye, we evaluated the incidence of severe anaphylactic reactions to isosulfan blue dye during the performance of sentinel lymph node biopsy for breast cancer at our institution. Methods: A retrospective chart review study enrolled 1,456 consecutive patients with breast cancer at our institution. Sentinel lymph node biopsy was performed using both isosulfan blue dye and technetium-99m sulfur colloid. Cases of anaphylaxis were reviewed in detail. Results: Overall, 12 (0.8%) of the 1,456 patients had severe anaphylactic reactions. All 12 patients experienced cardiovascular collapse (profound hypotension and tachycardia) and skin reactions; and patients required admission to an intensive care unit bed or equivalent setting for postoperative monitoring. No deaths or permanent disability occurred. Conclusions: Prompt recognition and aggressive treatment of anaphylactic reactions to isosulfan blue are critical to prevent an adverse outcome. Lymphatic mapping with blue dye should be performed in a setting where personnel are trained to recognize and treat anaphylaxis. J Curr Surg. 2018;8(3-4):32-34 doi: https://doi.org/10.14740/jcs365w

Protein-Losing Enteropathy in Patients With Congenital Heart Disease

BackgroundProtein-losing enteropathy (PLE), characterized by loss of proteins in the intestine, is a devastating complication in patients with congenital heart disease. The cause of PLE is unknown, but lymphatic involvement has been suspected. ObjectivesThe authors evaluated the use of lymphangiographic imaging and liver lymphatic embolization as a treatment for PLE. MethodsThis was a single-center, retrospective review of imaging and interventions used in 8 consecutive patients with liver lymphatic embolization and congenital heart disease with elevated central venous pressure complicated by PLE. ResultsLiver lymphangiography was performed in 8 patients (5 males, 3 females; median age, 21 years), 7 of whom demonstrated leakage of liver lymph into the duodenum through abnormal hepatoduodenal lymphatic communications. This was confirmed by duodenoscopy with simultaneous injection of isosulfan blue dye into the liver lymphatics in 6 of 7 patients. Liver lymphatic embolization with ethiodized oil in 2 patients resulted in a temporary increase in albumin blood level and symptom improvement in 1 patient, but was complicated by duodenal bleeding in both patients. Of the remaining 6 patients, liver lymphatic embolization with n-butyl cyanoacrylate glue resulted in sustained improvement of the serum albumin level and symptoms in 3 patients, temporary improvement in 2 patients, and no change in 1 patient with median follow-up of 135 days (range, 84 to 1,005 days). ConclusionsThe authors demonstrated liver lymph leakage as a cause of PLE in patients with congenital heart disease and elevated central venous pressure. Lymphatic embolization led to improved albumin levels and relief of symptoms. Further experience with the technique is needed to determine long-term outcome of this procedure.

Abstract P2-01-11: SentimagIC: A non-inferiority trial comparing super paramagnetic iron oxide vs. Tc99 and blue dye in the detection of axillary sentinel nodes in patients with early stage breast cancer

Abstract Background: Sentinel lymph node biopsy (SLNB), performed using radioisotope tracer with or without blue dye, is a highly accurate method for staging the axilla in early breast cancer. A radioisotope tracer with or without blue dye is the most commonly used technique for SLNB. Superparamagnetic iron oxide mapping agents detected by a handheld magnetic probe have been explored to overcome the disadvantages of the standard technique which include the short half-life, availability, handling and disposal issues for radioisotope, and the risk of allergic reactions to blue dye. Iron oxide mapping agents have been shown to be non-inferior to the standard technique in European studies. The SentimagIC trial was designed to establish the non-inferiority of a new formulation of the magnetic tracer, SiennaXP, to the combination of radioisotope and blue dye and was required to support a US regulatory submission. Methods: Between January and December 2015, 160 patients with clinically node negative early stage breast cancer were recruited from six centers in the United States. Subjects received radioisotope injection then an intraoperative subareolar injection of SiennaXP and isosulfan blue dye prior to SLNB being performed. The sentinel node identification rate was compared between SiennaXP and the standard technique to evaluate concordance and non-inferiority. Results: 147 procedures were completed in 147 subjects. A total of 369 histologically confirmed nodes were excised. The nodal detection rate was 94.3% (348/369) with SiennaXP and 93.5% (345/369) with the standard technique (difference 0.8%, 95% binomial confidence interval lower bound -2.1%). The per-subject detection rate was 99.3% (145/146) with SiennaXP and 98.6% (144/146) with the standard technique (one subject excluded due to not contributing any analyzable nodes). There were 22 subjects with positive SLNs, of whom 21 (95.4%) were detected by both SiennaXP and the standard tracers. In one subject, a positive node was not identified by any tracer, but was removed as clinically suspicious. The number of nodes excised per subject was 2.4 for both SiennaXP and for the standard combined technique. Conclusion: This study showed SiennaXP is non-inferior to the standard dual technique of radioisotope and blue dye for axillary sentinel lymph node detection in early stage breast cancer and this provides a potential alternative to radioisotope and blue dye. Citation Format: Alvarado M, Bold R, Gittleman M, Beitsch P, Blair S, Harmer Q, Kivilaid K, Teshome M, Thompson A, Mittendorf E, Hunt K. SentimagIC: A non-inferiority trial comparing super paramagnetic iron oxide vs. Tc99 and blue dye in the detection of axillary sentinel nodes in patients with early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-11.

Eight Years' Experience of Sentinel Lymph Node Biopsy in Melanoma Using Lymphoscintigraphy and Gamma Probe Detection After Radiocolloid Mapping.

Isosulfan blue dye peripheral injection is used in preoperative sentinel lymph node (SLN) identification alone or, to increase sensitivity, in conjunction with radiocolloid mapping. However, isosulfan blue dye has certain drawbacks and limitations. This study assesses the authors' experience of SLN biopsy using only radiocolloid tracer. Between 2000 and 2008, 218 patients underwent SLN biopsy with radiocolloid mapping, preoperative localization by lymphoscintigraphy and intraoperative confirmation by gamma probe in primary malignant cutaneous melanoma. Mean Breslow index was 2.1 mm. The SLN biopsy success rate was above 98% at all sites and 87% in head and neck locations. The 5-year overall survival rate was 90% and that of 5-year disease-free survival was 80%. False-negative rate, with a mean follow-up time of 41 months, was 5.5%. Sentinel lymph node biopsy can be successfully performed in patients with melanoma using only radiocolloid tracer without blue dye staining. In circumstances where blue dye cannot be used such as head and neck tumors, allergic reactions and pregnancy, radiocolloid tracer mapping alone is not a loss of chance for patients with melanoma.

Abstract OT2-02-03: Magnetic nano-device for identification of the breast sentinel nodes – A novel method

Abstract Breast sentinel node biopsy (SNB) is a well-established procedure that has supplanted traditional axillary dissection for most clinically node-negative breast cancer patients. Techniques to identify the draining lymph nodes include colored dyes and radioactive compounds. The Sentimag system uses a non-radioactive magnetic tracer and a handheld magnetic probe to identify sentinel nodes (SNs). The Sentimag Intraoperative Comparison (SentimagIC) study compares the magnetic technique with the standard combination of radioisotope and isosulfan blue dye. Methods: SiennaXP is a nano device composed of coated iron oxide nanoparticles designed to optimize lymphatic uptake and SN retention. The Sentimag breast SNB technique involves injection of 2cc of SiennaXP fluid into Sappey's subareolar plexus followed by 5 minutes of breast massage and an additional 15 minutes of time to optimize drainage prior to beginning the procedure. The Sentimag hand held probe is then used to identify a magnetic 'hotspot' through the skin of the axilla. The usual transverse axillary incision is made and the magnetometer is used to identify the SNs. The SentimagIC study involves utilizing the Sentimag technique in combination with the 'standard' techniques of isosulfan blue dye and 99technetium sulfur colloid. All blue, radioactive and magnetic SNs are removed and identified as stained blue (from isosulfan blue dye) or black/brown (from SiennaXP) or not, and both radioactive and magnetic counts are taken ex vivo on each node. Currently there are 6 active sites with a total of 60 patients enrolled. Trial design: This is a pivotal, prospective, open label, multicenter, paired comparison of the magnetic technique with the standard of care for lymph node localization in patients with breast cancer. Primary endpoints: The lymph node detection rate with SentiMag / SiennaXP and the detection rate with the standard of care; and the safety of Sentimag / SiennaXP as indicated by adverse events. Eligibility: Diagnosis of primary breast cancer or pure ductal carcinoma in situ (DCIS); Scheduled for sentinel lymph node biopsy; Clinical negative node status (i.e. T0-3, N0, M0). Statistical methods: The primary hypothesis is that the magnetic technique is non-inferior to the standard technique. Based on an expected detection rate of 95% for both techniques and a non-inferiority margin of 5%, 140 subjects will be required to show non-inferiority with 85% power. Discussion: SNB for breast cancer is a robust procedure, able to identify the draining lymph nodes of the breast in essentially all patients. Many techniques have been used including radioactive tracers (utilized on most cases) and colored dyes. SentiMag utilizes a unique nano device that can identify the same draining nodes but without the radioactivity used in most procedures. Radioactive dyes must be handled carefully to minimize radiation exposure to healthcare providers and the patient from the manufacturing process, delivery to facility, injection under a nuclear physician license, and the surgical procedure. This novel technique may supplant radioactive tracers allowing SNs to be removed without the patient/healthcare providers being exposed to radiation or the scheduling inconvenience of pre-procedure injection. Citation Format: Beitsch PD, Hunt KK, Bold RJ, Gittleman MA, Blair SL, Alvarado MD, Harmer QJ. Magnetic nano-device for identification of the breast sentinel nodes – A novel method. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-02-03.

Abstract P2-12-02: Axillary reverse mapping: A feasibility study

Abstract Background The mainstay of the therapy in breast cancer has been mastectomy or wide local excision along with axillary lymph node dissection (ALND). There are a lot of adverse effects associated with ALND, lymphedema being the most devastating. Sentinel lymph node biopsy (SLNB) can identify women who may or may not need axillary dissection and translate into a smaller number of patients undergoing axillary dissection. However, patients having positive lymph node on SLNB will still have to undergo ALND. To reduce the occurrence of lymphedema and its associated complications the technique of Axillary Reverse Mapping (ARM) has been developed. It is based on the hypothesis that the lymphatic pathway of the arm is not involved by the metastasis of the breast primary and after accurately identifying and preserving the arm lymphatics, there would be risk of neither lymphedema, nor leaving behind metastatic cells in the lymph nodes. This prospective study was carried out to evaluate the feasibility of ARM in patients undergoing ALND. Methods This prospective study was carried out in the Department of General Surgery, PGIMER, from July 2010 to Dec 2011. There were seventy five Biopsy/FNAC confirmed breast cancer female patients between 18 to 75 years. All patients were undergoing ALND as part of their treatment. Patients with any prior surgical treatment for primary invasive breast cancer, bilateral breast cancer and metastatic breast disease were excluded. Patients with heart diseases, active or uncontrolled infection, dementia, altered mental status or any psychiatric condition, pregnant or lactating women and with known allergies to blue dye were also excluded. All patients were treated as per the standard treatment for stage. All ALNDs were performed by a single surgeon. ARM was performed in all the patients by giving 5 ml of Isosulfan Blue Dye (Sterlized 1% solution) in the upper inner arm of the involved site approximately 60 minutes before exposure. Results The results were analyzed clinically during surgery and post-operatively by histo-pathological examination of lymphnodes. Intra-operatively, the identification of lymphnodes and lymphathics were noted in 17(22.7%) and 33 patients(44%) respectively. In none of the patient any attempt was made to preserve the blue nodes and all the lymph nodes were resected and sent for histopathological examination. In only 2 of 17 patients (11.76%) the lymph node was positive for malignant tumour cells. The tumour burden in both these patients was very high (more than 10 nodes involved). No association was found in the identification rates of ARM nodes and lymphatics to age, BMI, size of tumour, site of tumour, pathological status of axilla and timing of dye. Conclusion The identification rate of ARM lymphatics and nodes is low when only blue dye is used. The method appears it to be oncologically safe in patients with low tumour burden. However there is need for further studies will before this procedure can be universally applied without compromising the oncologic safety. Once the technique is proven to be oncologically safe even in a selected group of patients, a large randomized trial will be needed to give a satisfactory answer whether the problem of lymphedema be eliminated or minimized in the patients in whom arm lymphatics are successfully preserved. Citation Format: Khare S, Singh G, Das A, Bal A. Axillary reverse mapping: A feasibility study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-02.