Blue Dye Tracer Research Articles

Evaluation of traditional targeted axillary dissection eligibility criteria for node-positive breast cancer after neoadjuvant chemotherapy in a prospective multicenter registry

IntroductionTargeted axillary dissection (TAD) is performed after neoadjuvant systemic therapy (NST) to decrease the rate of non-therapeutic axillary dissection (ALND) for patients with node-positive breast cancer. In order to ensure the oncologic safety of TAD, eligibility criteria resulting in a low false negative rate (FNR) have been proposed. The purpose of this study was to evaluate the utility of the traditional criteria. MethodsData was collected from a prospective multicenter registry. In order to ascertain FNRs, pathologic findings in the sentinel lymph nodes (LN)s, malignant clipped LN, and axillary contents were determined. The FNRs within TAD eligibility criterion groups were compared. ResultsA total of 110 patients underwent TAD and ALND, and were therefore eligible for analysis. TAD retained a low FNR in advanced clinical T-N stage compared with earlier disease (T stage: 95% CI 0.00–11.93, p = 0.42; N stage: 95% CI 0.00–8.76, p = 0.31). Presentation with ≥4 abnormal LNs on axillary ultrasound did not predict a high TAD FNR (95% CI 0.00–5.37, p = 0.16). No significant differences were noted in TAD FNR when single was compared with dual tracer (blue dye vs dual tracer 95% CI 0.72–52.49, p = 0.13; radiotracer vs dual tracer 0.04–20.11, p = 0.51). Excision of the clipped LN and only one SLN was as accurate as excision of the clipped LN and ≥2 SLNs (95% CI 0.00–10.61, p = 0.38). ConclusionsTAD retained a low FNR among patients traditionally considered ineligible for this technique. However, excision of the clipped LN and at least one SLN remained essential to a low FNR.

Robotic para-aortic sentinel lymph node mapping in endometrial, cervical, and ovarian cancer.

The concept of pelvic sentinel lymph node mapping has been well-investigated in endometrial and cervical cancer. A variety of tracers have been used including blue dye, technetium-99-m (Tc-99m), and fluorescent tracer indocyanine green. Pelvic sentinel lymph node mapping has shown its safety, efficacy, and diagnostic accuracy, with high sensitivity and negative predictive value of more than 90%, in retrospective cohort studies as well as in prospective trials for robotic surgery. The concept of pelvic sentinel lymph node biopsy has been incorporated in several international guidelines in early-stage endometrial cancer and a subgroup of early-stage cervical cancer, although survival data are still needed to confirm its standard use. The application of para-aortic sentinel lymph node mapping is still in a development phase, but its detection rate and diagnostic accuracy seem to be promising in initial studies. Here, an overview is given of the recent developments in the different methodologies used for identifying para-aortic sentinel lymph nodes in endometrial, cervical, and ovarian cancer.

The application of contrast-enhanced ultrasound for sentinel lymph node evaluation and mapping in breast cancer patients.

To retrospectively investigate the application of contrast-enhanced ultrasound on sentinel lymph node (SLN-CEUS) for SLN evaluation and mapping in breast cancer patients. Patients diagnosed with breast cancer at the First Affiliated Hospital of Sun Yat-sen University from June 2019 to March 2021 were conveniently evaluated by SLN-CEUS. The results of SLN-CEUS and B mode-ultrasound (BUS) were collected and compared. For patients who only underwent SLN-CEUS, we conducted a 1:1 propensity score matching (PSM). The diagnostic parameters, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative rate (FNR), false positive rate (FPR), and proportion of undetermined diagnoses were compared between the SLN-CEUS and BUS cohorts. The identification rate and FNR of sentinel lymph node biopsy (SLNB) were also assessed. There were 327 patients in each of the SLN-CEUS and BUS cohorts. Among the entire cohort, both NPV [90.2% (95% CI, 85.4-93.5%) vs. 83.5% (95% CI, 77.8-88.0%), P=0.048] and accuracy [80.7% (95% CI, 76.5-85.0%) vs. 73.7% (95% CI, 68.9-78.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In non-neoadjuvant treatment (NAT) patients, the NPV [94.7% (95% CI, 89.9-97.4%) vs. 85.5% (95% CI, 79.1-90.2%), P=0.007] and accuracy [87.6% (95% CI, 83.2-92.0%) vs. 76.0% (95% CI, 70.4-81.5%), P<0.001] of SLN-CEUS were significantly higher than those of BUS. In NAT patients, no difference in diagnostic efficacy was found. The proportion of undetermined diagnoses of SLN-CEUS was significantly lower than that of BUS (5.8% vs. 15.3%, P<0.001). The identification rate of SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 94.2%, 96.3%, and 89.9%, respectively. The FNR of SLNB with the blue-dye tracer in combination with SLN-CEUS in overall patients, non-NAT patients, and NAT patients was 7.3%, 4.0%, and 12.5%, respectively. Compared to BUS, SLN-CEUS is a better technique for diagnosing SLNs in early breast cancer patients, showing superiority in multiple diagnostic parameters. However, the diagnostic value of SLN-CEUS in NAT patients is still undetermined. SLN-CEUS is a promising mapping method in SLNB, with a high identification rate and a low FNR when used in combination with a blue-dye tracer.

BLOOD-BRAIN BARRIER DYSFUNCTION IN WISTAR RATS EXPOSED TO MULTI-TRANSCEIVER MOBILE RADIOFREQUENCY, SOUND, AND VIBRATIONS

This study looked at the functional changes in the blood-brain barrier (BBB) in Wistar rats after exposure to electromagnetic field, vibration, and ringtone from a multi-transceiver mobile phone. Twenty-five (25) male Wistar rats were randomly divided into five groups (n=5). For six weeks, group A (control) and test groups were exposed to mobile phone electromagnetic field through a 10-minute calls/day from a Tecno 900/1800 MHz in various modalities. Viz: groups B – E in silent-only, vibration only, ringtone-only and ringtone with vibration, respectively. BBB in various regions of the brain using evans blue dye tracer technique and brain TNF-α was studied at the end of the sixth week of exposure. There were significant (α0.05) decrease in BBB in the cerebellum, cerebrum, and the two hemispheres of the brain and insignificant increases in the levels of brain TNF across all groups of animals exposed to phones in various modalities. These findings suggest that exposure to electromagnetic fields, vibration, and sound from multi-transceiver phones may be a risk factor for loss of BBB integrity.

Sentinel Lymph Node Identification in Patients With Breast Cancer Using Lymphosonography.

The objective of the work described here was to evaluate the efficacy of lymphosonography in identifying sentinel lymph nodes (SLNs) in patients with breast cancer undergoing surgical excision. Of the 86 individuals enrolled, 79 completed this institutional review board-approved study. Participants received subcutaneous 1.0-mL injections of ultrasound contrast agent (UCA) around the tumor. An ultrasound scanner with contrast-enhanced ultrasound (CEUS) capabilities was used to identify SLNs. Participants were administered with blue dye and radioactive tracer to guide SLN excision as standard-of-care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and UCA, and sent for pathology. Two hundred fifty-two SLNs were excised; 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Comparison with blue dye revealed accuracies of 96.2% for radioactive tracer and 99.4% for lymphosonography (p > 0.15). Relative to radioactive tracer, blue dye had an accuracy of 68.5%, and lymphosonography achieved 86.5% (p < 0.0001). Of 252 SLNs excised, 34 were determined to be malignant by pathology; 18 were positive for blue dye (detection rate=53%), 23 for radioactive tracer (detection rate=68%) and 34 for UCA (detection rate=100%) (p < 0.0001). Lymphosonography was similar in accuracy to radioactive tracer and higher in accuracy than blue dye in identifying SLNs. All 34 malignant SLNs were identified by lymphosonography.

Sentinel Lymph Node Identification in Post Neoadjuvant Chemotherapy Breast Cancer Patients Undergoing Surgical Excision Using Lymphosonography.

This study evaluated the efficacy of lymphosonography in the identification of sentinel lymph nodes (SLNs) in post neoadjuvant chemotherapy patients with breast cancer scheduled to undergo surgical excision. Seventy-nine subjects scheduled for breast cancer surgery with SLN excision completed this IRB-approved study, out of which 18 (23%) underwent neoadjuvant chemotherapy before surgery. Subjects underwent percutaneous Sonazoid (GE Healthcare) injections around the tumor area for a total of 1.0 mL. Lymphosonography was performed using CPS on an S3000 HELX scanner (Siemens Healthineers) with a linear probe. Subjects received blue dye and radioactive tracer as part of their standard of care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and Sonazoid. The results were compared between methods and pathology findings. Seventy-two SLNs were surgically excised from 18 subjects, 29 were positive for blue dye, 63 were positive for radioactive tracer and 57 were positive for Sonazoid. Comparison with blue dye showed that both radioactive tracer and lymphosonography achieved an accuracy of 53% (P > .50). Comparison with radioactive tracer showed that blue dye had an accuracy of 53%, while lymphosonography achieved an accuracy of 67% (P < .01). Of the 72 SLNs, 15 were determined malignant by pathology; the detection rate was 47% for blue dye (7/15), 67% for radioactive tracer (10/15) and 100% for lymphosonography (15/15) (P < .001). Lymphosonography achieved similar accuracy as radioactive tracer and higher accuracy than blue dye for identifying SLNs. The 15 SLNs positive for malignancy were all identified by lymphosonography.

Effects of Rourea coccinea ethanolic root extract on ovalbumin-induced allergic asthma in rats

Rourea coccinea (syn. Byrsocarpus coccineus) Schum. and Thonn. (Connaraceae) is a medicinal plant that is being used for the treatment of various disorders in Tropical Africa. Previously, we reported anti-inflammatory and antioxidant effects of ethanolic extract of R. coccinea root bark (EERc). The present study aimed to test protective potential effects of EERc treatments against ovalbumin-induced airway lung inflammatory and to investigate some of its possible underlying mechanism on allergic asthma. Rats were sensitized and challenged with ovalbumin (OVA), and were orally treated daily with EERc at 200, 400 and 800 mg/kg from day 24 to day 27 post sensitization. The number of total and differential inflammatory cells, leakage of Evans blue dye tracer, histamine and TNF-α level in bronchoalveolar lavage (BAL) fluid were measured. OVA instillation induced airway lung inflammation, which was significantly suppressed by pre-treatment with EERc. Analysis of bronchoalveolar lavage (BAL) revealed that EERc pre-treatment significantly inhibited leukocytosis and reduced Evans blue dye content in the BAL fluid. EERc also significantly decreased the production and release of histamine and TNF-α. Our study shows that EERc possesses significant anti-allergic activity which might be attributed to reduction of histamine, TNF-α in the BAL fluid.

A Randomized Prospective Non-Inferiority Trial of Sentinel Lymph Node Biopsy in Early Breast Cancer: Blue Dye Compared with Indocyanine Green Fluorescence Tracer.

Simple SummaryThis randomized study was conducted to evaluate sentinel lymph node biopsy with indocyanine green (ICG) compared with blue dye as a tracer in women with early breast cancer without any sign of lymph node invasion. ICG is a fluorescent tracer well known in medical practice for 50 years that is used as tracer of sentinel lymph nodes in numerous types of cancers other than breast cancer. This tracer is cheaper than radioactive tracers, with an easy learning curve.Background: Indocyanine green (ICG) is a promising tracer for sentinel lymph node biopsy in early breast cancer. This randomized study was conducted to evaluate sentinel lymph node biopsy with ICG compared with blue dye as a tracer in woman with early breast cancer without any sign of lymph node invasion. Methods: Between January 2019 and November 2020, 240 consecutive women with early breast cancer were enrolled and randomized to sentinel lymph node biopsy using ICG or blue dye. The primary endpoint was the sentinel lymph node detection rate in both arms. Results: ICG was used in 121 patients and detected sentinel lymph nodes in all patients (detection rate, 100%; 95% CI: 96.9–100.0) while blue dye was used in 119 patients and detected sentinel lymph nodes in 116 patients (detection rate: 97.5%, 95% CI: 92.9–99.1). This analysis indicated the non-inferiority of ICG vs. blue dye tracer (90%CI: −1.9–6.9; p = 0.0009). Conclusion: ICG represents a new promising tracer to detect sentinel lymph nodes in early breast cancer with a detection rate similar to other conventional tracers, and is associated with easy learning and low cost. Our result suggest that this technique is a good alternative to avoid radioactive isotope manipulation.

Role of Hormonal Receptor in Predicting Sentinel Lymph Node Metastasis in Early Breast Cancer.

Background:Sentinel lymph node biopsy is one of the minimally invasive techniques that can confirm the presence of metastasis of regional lymph nodes in cancer. Sentinel lymph node biopsy can be done with a lymph mapping technique using blue-dye, radiotracer, or a combination of both. In developing countries, sentinel lymph node biopsy is often done with a single agent, which is the blue dye. The limitation of conducting SLNB in Indonesia is the availability of patent blue dye and radioisotope tracer. To overcome that, a hormonal receptor is expected to aid in predicting sentinel lymph node metastasis.Objective:The aim of this study was to investigate the hormonal receptor as a prognostic factor of sentinel lymph node metastasis in breast cancer.Methods:This study was conducted in Universitas Sumatera Utara Teaching Hospital with the acknowledgment from the Ethics Committee of the respected hospital by the number of 116/KEP/USU/2020. Total of 51 patients participated in this research.Results:Statistically, the p-value in each immunohistochemistry group is > 0.05 in all ER (+) / PR (+); ER (+) / PR (-); ER (-) / PR (+) groups. This shows that there is no significant relationship between hormonal receptors on sentinel lymph node metastases.Conclusion:The statistical evaluation showed that there is no significant correlation between the hormonal receptor and sentinel lymph node metastasis (p>0.05), but is found clinically significant. Therefore, hormonal receptors should be considered as a predicting factor for sentinel lymph node metastasis.

Early Institutional Experience of Dual Tracer and Single-Photon Emission Computed-Tomography/Computed-Tomography Mapping for Sentinel Node Biopsy: A Report of Two Early-Stage Breast Cancer

Intraoperative sentinel lymph node mapping (SLNM) with methylene blue dye (MBD) tracer has been the recommended method to detect SLN in early-stage breast cancer patients in low-resource settings. However, the use of MBD alone is hampered by the high false-negative rate; thus, it requires coupling with other mapping methods if the appropriate infrastructure and services are available. In this article, we present two prospective cases detailing our initial experience using the gold-standard dual tracer technique (DTT: MBD and 99mTc-nanocolloid radioisotope) in combination with hybrid single-photon emission computed-tomography/computed-tomography (SPECT/CT) preoperative mapping for image-guided SLN biopsy (SLNB). Overall, both studies were successful in identifying the SLNs, which aided in mapping the possible anatomical spread of the disease.

Dung beetles as hydrological engineers: effects of tunnelling on soil infiltration

1. Soil infiltration capacity determines the partitioning of precipitation into infiltration and overland flow and is therefore an important soil hydrological characteristic. Water infiltration through soil is facilitated by macropores created by roots and soil macrofauna. In clay‐rich soils, such as those of the tropical forests of Sabah, Malaysian Borneo, most infiltration occurs via these preferential flow pathways.2. We evaluated the effects of dung beetle tunnelling on infiltration and macropore creation (depth and width of the flow pathways) in tropical forest soils in Sabah. Using mesocosms, we applied three treatments (i) soil‐only, (ii) dung‐only, (iii) dung + dung beetles, and measured saturated hydraulic conductivity (i.e., the steady‐state infiltration rate) after 0, 5 and 10 days, and assessed depth and width of infiltration pathways by applying a blue dye tracer.3. The steady‐state infiltration rate increased in the presence of dung beetles, though differences among treatments were only statistically significant after 10 days. After 5 days of dung beetle presence, infiltrated water had reached a greater depth than the control mesocosms without beetles. However, there were no differences in the width of infiltration pathways among treatments.4. These results reveal the important, but under studied roles of dung beetles on soil hydrological functioning, that may have consequences for nutrient cycling and plant productivity. Further, our findings indicate that the novel application of an established hydrological method—blue dye tracer—can provide interesting and reliable results for macrofauna–soil interaction studies.

Optimization of sentinel lymph node identification techniques in the Indian setting: A randomized clinical trial.

The recommended technique of sentinel lymph node biopsy (SLNB) in breast cancer is a combination of blue dye and radiotracer. In the Indian scenario, SLNB is still not routinely practiced due to lack of nuclear medicine facilities and unavailability of isosulfan blue or patent blue violet (PBV). This study was conducted for optimizing SLN identification techniques by comparing the identification rate using PBV and methylene blue (MB) in combination with radiotracer. Single-blinded two-arm parallel design randomized control trial was conducted at an apex teaching and research medical institute in India. Patients with axillary LN-negative breast cancer were included. Blue dye and radio tracer were injected preoperatively, and SLNB was performed using a combination technique. Frozen section was performed. Demographic, clinical, radiological, operative, and histopathological data were recorded. Descriptive statistics were used to represent patient characteristics. Baseline characteristics for entire cohort and between groups were compared using Student's t-test for quantitative variables and Chi-square test for qualitative variables. A total of 119 patients were randomized for mapping with MB and 118 patients with PBV between 2011 and 2015. SLN was identified in 116 patients with MB and 115 with PBV. SLN identification proportions were 97.4% (MB) and 96.6% (PBV). In patients undergoing axillary lymph node dissection, concordance with SLNB was 98.5% and 96.61% in MB and PBV, respectively. False-negative proportion for MB was 2.56% and 7.69% for PBV, respectively. The cost of MB is about INR 15 per ~10-mL vial. The cost of PBV is approximately ~$91 per ampoule (equivalent to approximately INR 8190). SLNB using MB can be recommended as the technique of choice in low-resource settings.

Biogas Digestate Application Modifies Solute Transport Conditions in Soils and Increases the Release of Phosphorus

Core Ideas Severe rainfall events cause increased phosphorus release from soils. The proportion of DRP increases with increasing rainfall duration. Digestate application causes a 400‐fold increase in pore water P concentrations. The DRP fraction is clearly dominant immediately after fertilization. Digestate application facilitates a flux regime shift with preferential flow pathways. The application of fertilizers to soils may impair the quality of both surface and subsurface waters. Severe rainfall events that follow fertilizer application can increase P release from soils. In this study, suction plates were installed in a loamy soil with the aim of determining the P transport patterns and processes in the soil before and after the application of biogas digestate. Prior to the application of biogas digestate, the pore water concentrations of dissolved reactive P (DRP) were significantly lower than the total P (TP) concentrations, with DRP/TP ratios increasing from 0.03 to 0.89. After fertilizer application, the TP and DRP pore water concentrations increased 400‐fold. The DRP/TP ratio remained almost constant at 0.83. After 220 mm of precipitation, 4.5% of the P mass applied was leached to below the 50‐cm soil depth, indicating the general mobility of P in soils during high‐intensity rainfall. Brilliant Blue dye tracing experiments revealed that organic‐matter‐rich biogas digestate obviously changes the flow and transport patterns in soils from being homogenous to moderately heterogeneous, including preferential flow. Although the P loading across the flux plane had been equilibrated prior to treatment, after the application it was found to be concentrated in preferred transport regions. The emerging conclusion is that the risk of ground and subsequent surface water pollution with P after fertilization with biogas digestate originates not only from the applied P mass but also from the shift in the flow and transport regime caused by the organic‐matter‐rich slurry.

Assessment of Nitrogen and Phosphorus Pathways at the Profile of Over-fertilised Alluvial Soils. Implications for Best Management Practices

Contrasting soil profiles (coarse-textured and fine-textured) treated with brilliant blue (BB) dye tracer, inorganic nitrogen (N) and phosphorus (P) concentrations along and between stained preferential flow pathways were examined for an irrigated and overfertilised maize monoculture system at the Mediterranean central Chile. The PO4-P concentrations were 2- to 10-fold higher in areas with BB than in areas without BB below 0.5-m soil depth in both soils. This elevated concentration was attributed to transport through cracks in fine-textured soil and finger flow in coarse-textured soil. The highest PO4-P value (13 mg kg−1) was found in areas with BB at the fine-textured soil. There were no significant differences in inorganic N concentration between areas with and without BB for both soils, which suggest that the effects of preferential flow are less important for inorganic N forms. There was a strong significant (p < 0.01) positive correlation between PO4-P and NH4-N concentrations in the fine-textured soil, and the amounts retained were clearly proportional to the clay content. Strategies for reducing N and P losses must be placed on good agronomic management of irrigated maize cropping system including accurate calculation of N and P fertiliser rates and establishment of suitable mitigation measures such as cover cropping.

Effect of stand origin and slope position on infiltration pattern and preferential flow on a Loess hillslope

AbstractPreferential flow is expected to provide an important pathway to replenish soil water at deep soil layers in arid or semiarid areas; however, few studies have addressed this topic, especially in semiarid Loess hillslopes. This study aimed to quantify the effect of stand origin and slope position on the contribution of preferential flow to total infiltration and spatial variations in water flow. A blue dye tracer experiment was conducted to visualize water flow in Robinia pseudoacacia plantation (PL), natural forestland (NF), and natural grassland (NG) at the upslope, midslope, and downslope, and semivariance analysis was used to determine spatial variability at the centimeter scale. The results showed that role of macropore flow was dominant in upslope and midslope, and larger in NF than that in PL and NG, due to presence of abundant root systems in the upper soil of NF. Moreover, contribution of preferential flow at the upper slope in NF was larger than that in PL. At the downslope, the role of rock fragments coverage at the downslope was emphasized, leading lateral flow dominant at the downslope in PL and NG. In addition, contribution of preferential flow and vertical variability of infiltration at the downslope in PL was higher than that in NF. The findings demonstrate that compared with PL, NF has a more positive impact on increasing infiltration and preferential flow that can replenish deep soil water, and reducing surface runoff and soil erosion. The presence of rock fragments coverage can make lateral flow dominant at the downslope on the Loess hillslope, related to water movement along the slope toward streams and catchment outlets.

Handheld magnetic probe with permanent magnet and Hall sensor for identifying sentinel lymph nodes in breast cancer patients

The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet. Numerical and experimental results show that the longitudinal detection length is approximately 10 mm, for 140 μg of iron. Clinical tests were performed, for the first time, using magnetic and blue dye tracers—without radioisotopes—in breast cancer patients to demonstrate the performance of the probe. The nodes were identified through transcutaneous and ex-vivo measurements, and the iron accumulation in the nodes was quantitatively revealed. These results show that the handheld magnetic probe is useful in sentinel lymph node biopsy and that magnetic techniques are widely being accepted as future standard methods in medical institutions lacking nuclear medicine facilities.

66PD Comparison of blue dye and radio-tracer markers for identification of axillary sentinel node in patients with early breast cancer

Background Sentinel lymph node biopsy is a standard procedure in treatment of early breast cancer. However, the technique itself and the use of lymphatic markers remain generally unstandardized. Aim of this study is to compare efficacy of sentinel node biopsy using methylene-blue dye, radioactive colloid and dual marker technique. Methods Prospective study includes patients with early breast cancer treated in a single institution from year 2013 to 2015. Three subgroups were created according to the method of lymphatic marking (A¼blue dye, B¼radioactive technetium, C¼dual markers). Sentinel identification rate and the number of marked sentinel nodes was compared between groups. Concordance between two lymphatic markers was assessed using Cochrane’s Kappa statistical method. Results Study includes total of 204 patients. Sentinel node identification rate (95% CI) was 87.4% (þ/- 6.5%) in group A, 94.1% (þ/-8.7%) in B and 100% (þ/- 2.6%) in group C. Median number of marked nodes was one node. There were more hot nodes in group C than in groups A and B (P¼0.002). In group C, concordance index between blue dye and radioactive tracer was relatively weak (kappa¼0.049, 95% CI 0-0.244). Conclusions: Radioactive tracer can be used as single lymphatic marker, however, for best results dual marking is recommended. Methylene blue dye and radioactive Technecium colloid can be considered as complimentary when used simultenously. The use of blue dye as a single lymphatic marker is not recommended because of unacceptably low sentinel identification rate. Legal entity responsible for the study : N/A Funding: N/A Disclosure All authors have declared no conflicts of interest.

Prospective study found that peripheral lymph node sampling reduced the false-negative rate of sentinel lymph node biopsy for breast cancer.

BackgroundAlthough sentinel lymph node biopsy (SLNB) can accurately predict the status of axillary lymph node (ALN) metastasis, the high false-negative rate (FNR) of SLNB is still the main obstacle for the treatment of patients who receive SLNB instead of ALN dissection (ALND). The purpose of this study was to evaluate the clinical significance of SLNB combined with peripheral lymph node (PLN) sampling for reducing the FNR for breast cancer and to discuss the effect of “skip metastasis” on the FNR of SLNB.MethodsAt Shandong Cancer Hospital Affiliated to Shandong University between March 1, 2012 and June 30, 2015, the sentinel lymph nodes (SLNs) of 596 patients with breast cancer were examined using radiocolloids with blue dye tracer. First, the SLNs were removed; then, the area surrounding the original SLNs was selected, and the visible lymph nodes in a field of 3–5 cm in diameter around the center (i.e., PLNs) were removed, avoiding damage to the structure of the breast. Finally, ALND was performed. The SLNs, PLNs, and remaining ALNs underwent pathologic examination, and the relationship between them was analyzed.ResultsThe identification rate of SLNs in the 596 patients was 95.1% (567/596); the metastasis rate of ALNs was 33.7% (191/567); the FNR of pure SLNB was 9.9% (19/191); and after the SLNs and PLNs were eliminated, the FNR was 4.2% (8/191), which was significantly decreased compared with the FNR before removal of PLNs (P = 0.028). According to the detected number (N) of SLNs, the patients were divided into four groups of N = 1, 2, 3, and ≥4; the FNR in these groups was 19.6, 9.8, 7.3, and 2.3%, respectively. For the patients with ≤2 or ≤3 detected SLNs, the FNR after removal of PLNs was significantly decreased compared with that before removal of PLNs (N ≤ 2: 14.0% vs. 4.7%, P = 0.019; N ≤ 3: 12.2% vs. 4.7%, P = 0.021), whereas for patients with ≥4 detected SLNs, the decrease in FNR was not statistically significant (P = 1.000). In the entire cohorts, the “skip metastasis” rate was 2.5% (15/596); the FNR caused by “skip metastasis” was 2.1% (4/191).ConclusionsThe FNR of SLNB was associated with the number of SLNs. For patients with ≤3 detected SLNs, PLN sampling can reduce the FNR of SLNB to an acceptable level of less than 5%. Because of the existence of the “skip metastasis” and distinct metastasis patterns, the FNR of SLNB cannot be completely eliminated.

Abstract OT3-02-02: ROSCO: A randomised phase III, stratified CEP17/TOP2A biomarker trial of neo-adjuvant 5-flourouracil, epirubicin and cyclophosphamide vs docetaxel and cyclophosphamide chemotherapy

Abstract Background: Patients with high risk early breast cancer undergoing chemotherapy are frequently treated with both anthracycline and taxane-based chemotherapy exposing patients to multiple toxicities. Molecular predictors of response to specific chemotherapy agents are emerging. Abnormal duplication of the centromeric region of chromosome 17 (CEP17) and either Topoisomerase 2A (TOP2A) gene amplification or deletion, have been identified in a recent meta-analysis as potent markers of anthracycline sensitivity (Bartlett et al JCO 2015). The ROSCO study has been designed to prospectively test the utility of these markers to select anthracycline or taxane based chemotherapy in the neoadjuvant setting. Key entry criteria: Confirmed invasive breast cancer; centrally confirmed CEP17 duplication and TOP2A status; primary tumour&amp;gt;2cms or documented axillary node metastasis Exclusion criteria include breast cancer with good risk features i.e. Grade 1/2 ER PR rich (Q score 7/8), HER2 negative tumours. Study treatment: Patients will undergo central testing for CEP-17 and TOP2A and be randomised to 4 cycles of FEC100 (5-Flourouracil 500mg/m2 Epirubicin 100mg/m2 cyclophosphamide 600mg/m2) or 4 cycles of TC (Docetaxel 75mg/m2 Cyclophosphamide 600 mg/m2). Following chemotherapy patients will undergo surgical resection, (Institutional standard). Patients with residual invasive cancer will receive 4 cycles of the alternative chemotherapy to that received in the neoadjuvant setting. HER2 positive patients will receive concurrent trastuzumab and continue standard adjuvant trastuzumab. . Patients with biopsy proven axillary node metastases will undergo combined blue dye and radioisotope tracer guided sentinel lymph node biopsy (SLNB) and axillary lymph node clearance as a single procedure during breast surgery. Adjuvant endocrine and radiation therapy will be Institutional standard Endpoints: The primary endpoint is pathological complete response (no invasive disease in breast or axilla (pCR)). Secondary endpoints include: clinical and radiological response; rate of breast conservation; patient reported outcomes; safety, tolerability and long term outcomes. In patients with proven nodal involvement the false negative rate of a negative post treatment SLNB compared to axillary node clearance will be reported. Sample size and stratification: 1050 patients will be randomised in a 1:1 ratio stratified by nodal status, ER, HER2, and biomarker status (CEP-17 amplified or TOP2A amplified/deleted) vs normal (CEP-17 normal TOP2A normal). Analysis: The primary analysis will assess the interaction between the treatment effect and CEP17/TOP2A status to determine if a differential treatment effect exists between CEP17/TOP2A Normal and CEP17/TOP2A Abnormal patients. pCR will be analysed using a logistic regression model including co-variates for treatment, CEP17/TOP2A status and an interaction term of the two effects Sample size is based on the ability to detect an absolute improvement in pCR in the biomarker abnormal group from 21% in the TC treated group to 30% in the FEC treated group. With 90% power at 10% significance level. Contact Information: the ROSCO Trial Office ROSCO@trials.bham.ac.uk. Citation Format: Rea DW, Haywood L, Francis AM, Bowden SJ, Brookes CM, MacKenzie M, Cameron D, Stein R, Earl HM, Thomas J, Abraham J, Stanley A, Starczinski J, McGoldrick T, Treharne-Jones P, Billingham L, Bartlett JM. ROSCO: A randomised phase III, stratified CEP17/TOP2A biomarker trial of neo-adjuvant 5-flourouracil, epirubicin and cyclophosphamide vs docetaxel and cyclophosphamide chemotherapy. [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 OT3-02-02.

Visualization of surfactant solution transport in saturated soil: an experimental study to represent wastewater loss from sewers

Surfactants are the main active agents in detergents products. Our investigation dealt with the effects of surfactants as a wastewater constituent on the infiltration process of wastewater through saturated soil. In order to more closely observe the flow’s interaction, in a laboratory experiment, a 2D Plexiglas model was filled with fine-grained soil and saturated with degassed water. The particle-free artificial laboratory wastewater was created by adding a commercially available detergent to degassed tap water producing a surfactant concentration with the strength equivalent of up to about 15 times of its critical micelle concentration. The visualization of flow was improved by adding a brilliant blue dye tracer enhancing the color contrast. Photographs were taken from the 2D model using conventional imaging equipment and were processed by image analysis to distinguish the dynamic flow interface between dyed and non-dyed areas. Primarily, the images of vertical flows were analyzed after reducing the contrast range. Next, utilizing an image analysis method, 2D images were reconstructed into 3D visualization models. Three-dimensional and cross-sectional images of the fluid–fluid–soil boundary layer revealed a rapid solute transport prevailing at the dynamic interfaces. This was confirmed with image analysis showing geometric irregularities on the soil surface.