Non-invasive predictors of axillary lymph node burden in breast cancer: a single-institution retrospective analysis.

PURPOSE: Axillary staging is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SNB) is currently used to stage patients who are clinically and radiologically node-negative. Since the establishment that axillary node clearance (ANC) does not improve overall survival in breast-conserving surgery for patients with low-risk biological cancers, axillary management has become increasingly conservative. This study aims to identify and assess the clinical predictive value of variables that could play a role in the quantification of axillary burden, including the accuracy of quantifying abnormal axillary nodes on ultrasound. METHODS: A retrospective analysis was conducted of hospital data for female breast cancer patients receiving an ANC at our centre between January 2018 and January 2020. The reference standard for axillary burden was surgical histology following SNB and ANC, allowing categorisation of the patients under 'low axillary burden' (2 or fewer pathological macrometastases) or 'high axillary burden' (> 2). After exploratory univariate analysis, multivariate logistic regression was conducted to determine relationships between the outcome category and candidate predictor variables: patient age at diagnosis, tumour focality, tumour size on ultrasound and number of abnormal lymph nodes on axillary ultrasound. RESULTS: One hundred and thirty-five patients were included in the analysis. Logistic regression showed that the number of abnormal lymph nodes on axillary ultrasound was the strongest predictor of axillary burden and statistically significant (P = 0.044), with a sensitivity of 66.7% and specificity of 86.8% (P = 0.011). CONCLUSION: Identifying the number of abnormal lymph nodes on preoperative ultrasound can help to quantify axillary nodal burden and identify patients with high axillary burden, and should be documented as standard in axillary ultrasound reports of patients with breast cancer.

Do soil property variations affect dicyandiamide efficiency in inhibiting nitrification and minimizing carbon dioxide emissions?

Nitrification inhibitors (NIs) are used to retard the nitrification process and reduce nitrogen (N) losses. However, the effects of soil properties on NI efficacy are less clear. Moreover, the direct and indirect effects of soil property variations on NI efficiency in minimizing carbon dioxide (CO2) emissions have not been previously studied. An incubation experiment was conducted for 40 days with two treatments, N (200 mg N-urea kg-1) and N + dicyandiamide (DCD) (20 mg DCD kg-1), and a control group (without the N) to investigate the response of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to DCD application and the consequences for CO2, nitrous oxide (N2O) and ammonia (NH3) emissions from six soils from the Loess Plateau with different properties. The nitrification process completed within 6-18 days for the N treatment and within 30->40 days for the N + DCD treatment. AOB increased significantly with N fertilizer application, while this effect was inhibited in soils when DCD was applied. AOA was not sensitive to N fertilizer and DCD application. The nitrification rate was positively correlated with the clay (p < 0.05) and SOM contents (p < 0.01); DCD was more effective in loam soil with low SOM and high soil pH. Soil pH significantly was decreased with N fertilizer application, while it increased when DCD was applied. Moreover, DCD application decreased CO2 emissions from soils by 22%-172%; CO2 emissions were negatively correlated with the clay and SOM contents. DCD application decreased N2O emissions in each soil by 1.0- to 94-fold compared with those after N fertilizer application. In contrast, DCD application increased NH3 release from soils by 59-278%. NH3 volatilization was negatively correlated with clay (p < 0.05) and SOM (p < 0.01) contents and positively correlated with soil pH (p < 0.01). Therefore, soil texture, SOM and soil pH have significant effects on the DCD performance, nitrification process and gaseous emissions.

Residual effects of tobacco biochar along with different fixing agents on stabilization of trace elements in multi-metal contaminated soils.

The residual effect of tobacco biochar (TB ≥ 500°C) mono and co-application with Ca-hydroxide (CH), Ca-bentonite (CB) and natural zeolite (NZ) on the bio-availability of trace elements TE(s) in alkaline soils has not been deeply studied yet. A pot study that had earlier been investigated TB mono and blended with CH, CB and NZ on the immobilization of Pb, Cu Cd, and Zn by Chinese cabbage. Maize crop in the rotation was selected as test plant to assess the residual impact of amendments on stabilization of Pb, Cu Cd, and Zn in mine polluted (M-P), smelter heavily and low polluted (S-HP and S-LP, respectively) soils. The obtained results showed that stabilization of Pb, Cd, Cu and Zn reached 63.84% with TB + CB, 61.19% with TB + CH, 83.31% with TB + CH and 35.27% with TB + CH for M-P soil, 36.46% with TB + NZ, 38.46% with TB + NZ, 19.40% with TB + CH and 62.43% with TB + CH for S-LP soil, 52.94% TB + NZ, 57.65% with TB + NZ, 52.94% with TB + NZ, and 28.44% with TB + CH for S-LP soil. Conversely, TB + CH and TB alone had mobilized Pb and Zn up to 19.29% and 34.96% in M-P soil. The mobility of Zn reached 8.38% with TB + CB and 66.03% with TB for S-HP and S-LP soils. The uptake and accumulation of Pb, Cd, Cu and Zn in shoot and root were reduced in three polluted soils. Overall, the combination of TB along with CH, CB and NZ has been proven to be effective in Pb, Cd, Cu and Zn polluted mine/smelter soils restoration.

Is sentinel node biopsy necessary in the radiologically negative axilla in breast cancer?

PURPOSE: The steady move towards axillary conservatism in breast cancer is based on studies demonstrating that axillary node clearance affords no survival benefit in a subset of patients with a positive pre-operative axillary ultrasound (AUS). However, less attention has been paid to AUS-negative patients who receive sentinel node biopsy as standard. METHODS: Previously assembled systematic review data was reassessed to evaluate nodal burden amongst patients with breast cancer and a clinically and radiologically negative axilla. RESULTS: Pooled data from four cohort studies reporting pre-operative axillary ultrasound in 5139 patients with breast cancer show it has a negative predictive rate of 0.951 (95% confidence interval 0.941-0.960). CONCLUSIONS: Reconsidering the use of ultrasound in patients with early breast cancer and non-palpable axillae reveals that sentinel node biopsy itself may represent surgical over-treatment in patients with a negative axillary ultrasound. The implications of this on the future of surgical management of the axilla are discussed.

Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients.

BACKGROUND: Management of the axilla in breast cancer is becoming increasingly conservative. Patients identified with a low axillary nodal burden (two or fewer involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node clearance (cANC). 'Fast track' to ANC in patients with involved nodes on pre-operative ultrasound may be over-treating a subgroup of these patients with low nodal burden, which would have precluded their need for ANC. This systematic review assesses the proportion of patients with involved nodes on pre-operative axillary ultrasound, which would fit low axillary burden criteria. METHODS: Meta-analysis of studies comparing axillary burden of breast cancer patients identified as pre-operative ultrasound negative versus positive was performed. The primary outcome measure was the number of patients with two or fewer involved nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals (CIs), means and probabilities of identifying two or fewer involved nodes versus greater than two were calculated. RESULTS: Six studies reported the axillary burden in 4271 patients who were either directed straight to ANC or cANC after SNB. There was a significantly greater axillary burden in the ultrasound positive versus negative groups (OR 5.95, 95% CI 5.80-6.11) with mean nodal retrieval values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively. Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of ultrasound positive patients possessed low axillary burden. CONCLUSIONS: Pre-operative ultrasound positive patients have significantly higher axillary burden. However, nearly half do fit the criteria of low axillary burden and could be considered for omission of ANC.

Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis.

PURPOSE: Breast-conserving surgery is effective for breast cancer treatment but is associated with morbidity in particular high re-excision rates. We performed a systematic review and meta-analysis to assess the current evidence for clinical outcomes with minimally invasive ablative techniques in the non-surgical treatment of breast cancer. METHODS: A systematic search of the literature was performed using PubMed and Medline library databases to identify all studies published between 1994 and May 2016. Studies were considered eligible for inclusion if they evaluated the role of ablative techniques in the treatment of breast cancer and included ten patients or more. Studies that failed to fulfil the inclusion criteria were excluded. RESULTS: We identified 63 studies including 1608 patients whose breast tumours were treated with radiofrequency (RFA), high intensity focussed ultrasound (HIFU), cryo-, laser or microwave ablation. Fifty studies reported on the number of patients with complete ablation as found on histopathology and the highest rate of complete ablation was achieved with RFA (87.1%, 491/564) and microwave ablation (83.2%, 89/107). Short-term complications were most often reported with microwave ablation (14.6%, 21/144). Recurrence was reported in 24 patients (4.2%, 24/570) and most often with laser ablation (10.7%, 11/103). The shortest treatment times were observed with RFA (15.6 ± 5.6 min) and the longest with HIFU (101.5 ± 46.6 min). CONCLUSION: Minimally invasive ablative techniques are able to successfully induce coagulative necrosis in breast cancer with a low side effect profile. Adequately powered and prospectively conducted cohort trials are required to confirm complete pathological ablation in all patients.

Magnetic sentinel lymph node biopsy in a murine tumour model.

The magnetic technique for sentinel node biopsy provides a radioisotope-free alternative for staging breast cancer. It requires refinement to reduce "residual iron content" at injection sites by maximising lymphatic uptake to prevent "void artefacts" on magnetic resonance imaging (MRI), which could adversely affect clinical use. The site and timing of injection of magnetic tracer was evaluated in a murine tumour model (right hind limb) in 24 wild type mice. Right-sided intratumoural and left sided subcutaneous injection of magnetic tracer and assessment of nodal iron uptake on MRI, surgical excision and histopathological grading at time frames up to 24 hours were performed. Rapid iron uptake on MRI, smaller "void artefacts"(P<0.001) and a significant increase in iron content with time were identified in the subcutaneous injection group (r=0.937; P<0.001).Subcutaneous injection and increasing delay between tracer injection and surgery is beneficial for lymphatic iron uptake. FROM THE CLINICAL EDITOR: Sentinel lymph node biopsy (SLNB) has been the standard of care in breast cancer management for some time. Recent development has seen the introduction of magnetic tracer for SLNB. In this article, the authors investigated the refined use of magnetic tracer in determining the optimal timing of administration and the location of injection. The findings should provide more data on the future use of this new technique.

Optimising magnetic sentinel lymph node biopsy in an in vivo porcine model.

The magnetic technique for sentinel lymph node biopsy (SLNB) has been evaluated in several clinical trials. An in vivo porcine model was developed to optimise the magnetic technique by evaluating the effect of differing volume, concentration and time of injection of magnetic tracer. A total of 60 sentinel node procedures were undertaken. There was a significant correlation between magnetometer counts and iron content of excised sentinel lymph nodes (SLNs) (r=0.82; P<0.001). Total number of SLNs increased with increasing volumes of magnetic tracer (P<0.001). Transcutaneous magnetometer counts increased with increasing time from injection of magnetic tracer (P<0.0001), plateauing within 60min. Increasing concentration resulted in higher iron content of SLNs (P=0.006). Increasing magnetic tracer volume and injecting prior to surgery improve transcutaneous 'hotspot' identification but very high volumes, increase the number of nodes excised. FROM THE CLINICAL EDITOR: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging of breast cancer patients. Although the current gold standard technique is the combined injection of technetium-labelled nanocolloid and blue dye into the breast, the magnetic technique, using superparamagnetic carboxydextran-coated iron oxide (SPIO), has also been demonstrated as a feasible alternative. In this article, the authors set up to study factors in order to optimize the magnetic tracers.

Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review.

The existing standard for axillary lymph node staging in breast cancer patients with a clinically and radiologically normal axilla is sentinel lymph node biopsy with a radioisotope and blue dye (dual technique). The dependence on radioisotopes means that uptake of the procedure is limited to only about 60% of eligible patients in developed countries and is negligible elsewhere. We did a systematic review to assess three techniques for sentinel lymph node biopsy that are not radioisotope dependent or that refine the existing method: indocyanine green fluorescence, contrast-enhanced ultrasound using microbubbles, and superparamagnetic iron oxide nanoparticles. Our systematic review suggested that these new methods for sentinel lymph node biopsy have clinical potential but give high levels of false-negative results. We could not identify any technique that challenged the existing standard procedure. Further assessment of these techniques against the standard dual technique in randomised trials is needed.

Sentinel lymph node identification rates and axillary concordance can only be accurately determined by comparing 'like with like' injected materials.

PURPOSE: Despite the accepted status of sentinel lymph node biopsy (SLNB) as the standard for axillary staging in breast cancer patients with clinically and radiologically negative axillae pre-operatively, there is surprisingly still a lack of consensus on the most appropriate site of injection of radioactive tracer with or without blue dye. METHODS: We discuss the article by Sadeghi et al. "Axillary concordance between superficial and deep sentinel node mapping material injections in breast cancer patients: systematic review and meta-analysis of the literature." Breast Cancer Res Treat 144(2): 213-222. RESULTS: Whilst in this study both comparison arms (superficial and deep injections) were in the same patients to ensure comparability of evaluated groups, this does limit the conclusions, which can be drawn from this study. It has meant that when comparing intra-operative sentinel lymph node (SLN) identification and concordance rates, it is not possible to compare 'like with like' at different injection sites (deep radioactive tracer vs superficial radioactive tracer; superficial blue dye vs deep blue dye). This leads to inaccurate conclusions due to the different properties of these materials. CONCLUSIONS: The only way to determine the optimal injection site of radioactive tracer and blue dye for SLN identification intra-operatively and accurate concordance rates is by direct comparisons of 'like with like' when it comes to injected materials at different injection sites.

Undifferentiated Pleomorphic Sarcoma Mimicking Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant augmentation is a low-risk procedure with few life-threatening complications, most commonly rupture or leakage and contraction of the capsule. Breast implant-associated (BIA) malignancies are rare. Anaplastic large cell lymphoma (ALCL) is the most well-known neoplastic condition associated with breast augmentation. Carcinomas arising in association with implants have been reported but are rarer than ALCL. BIA-mesenchymal tumors are extremely rare and most are locally aggressive fibromatosis. To date, only eight cases of BIA sarcomas have been reported. Herein, we describe a case of silicone BIA-undifferentiated pleomorphic sarcoma (UPS) that was initially mistaken for ALCL because of a significant clinical and radiological overlap in presentation and imaging. Here, we present the morphological and molecular features of this rare neoplasm. We reviewed the existing literature related to BIA sarcomas to highlight the importance of considering this diagnosis in cases of recurrent ALCL-negative BIA effusions.

Systematic review of radioguided versus wire-guided localization in the treatment of non-palpable breast cancers.

One-third of breast cancers present as non-palpable lesions. The current gold standard treatment for these cancers is localized wide local excision using wire-guided localization (WGL). WGL has drawbacks including technical and scheduling issues resulting in the development of alternative radioguided techniques (RGL). A systematic review was performed to identify studies comparing RGL and WGL. The outcomes of surgical margin status, re-operation rates, surgical operative time, volume and excised specimen weight and successful sentinel lymph node biopsy (SLNB) rates were evaluated. Pooled odds ratios (ORs) and 95 % confidence intervals were estimated using fixed-effects analyses and random-effects analyses in case of statistically significant heterogeneity (p < 0.05). Seven randomized controlled trials (RCTs) matching the inclusion criteria were identified. The pooled ORs for involved surgical margin status were 0.78 (95 % CI, 0.52-1.17); for re-operations 0.74 (95 % CI, 0.49-1.11) and for successful SLNB 1.29 (95 % CI, 0.66-2.53). There was a significant difference in surgical operating time in favour of RGL (mean difference (MD), -2.95; 95 % CI, -4.43, -1.47) and a significant difference in excised specimen volume, favouring WGL (MD, 6.79; 95 % CI, 0.03, 13.56). The MD for a specimen weight of -3.00 (95 % CI, -15.15, 9.15) showed no significant difference between RGL and WGL. RGL has a reduced operating time, but larger volume excisions compared to WGL. There is insufficient evidence to support the uptake of RGL over WGL, and larger, adequately powered, multi-centre RCTs are required.

Magnetic sentinel lymph node biopsy and localization properties of a magnetic tracer in an in vivo porcine model.

The standard for the treatment of early non-palpable breast cancers is wide local excision directed by wire-guided localization and sentinel lymph node biopsy (SLNB). This has drawbacks technically and due to reliance upon radioisotopes. We evaluated the use of a magnetic tracer for its localization capabilities and concurrent performance of SLNB using a handheld magnetometer in a porcine model as a novel alternative to the current standard. Ethical approval by the IRCAD Ethics Review Board, Strasbourg (France) was received. A magnetic tracer was injected in varying volumes (0.1-5 mL) subcutaneously into the areolar of the left and right 3rd inguinal mammary glands in 16 mini-pigs. After 4 h magnetometer counts were taken at the injection sites and in the groins. The magnetometer was used to localize any in vivo signal from the draining inguinal lymph nodes. Magnetic SLNB followed by excision of the injection site was performed. The iron content of sentinel lymph nodes (SLNs) were graded and quantified. All excised specimens were weighed and volumes were calculated. Univariate analyses were performed to evaluate correlation. Magnetic SLNB was successful in all mini-pigs. There was a significant correlation (r = 0.86; p < 0.01) between magnetometer counts and iron content of SLNs. Grading of SLNs on both H&E and Perl's staining correlated significantly with the iron content (p = 0.001; p = 0.003) and magnetometer counts (p < 0.001; p = 0.004). The peak counts corresponded to the original magnetic tracer injection sites 4 h after injection in all cases. The mean volume and weight of excised injection site specimens was 2.9 cm(3) (SD 0.81) and 3.1 g (SD 0.85), respectively. Injection of ≥0.5 mL magnetic tracer was associated with significantly greater volume (p = 0.05) and weight of excision specimens (p = 0.01). SLNB and localization can be performed in vivo using a magnetic tracer. This could provide a viable alternative for lesion localization and concurrent SLNB in the treatment of non-palpable breast cancer.

Preclinical studies of the role of iron oxide magnetic nanoparticles for nonpalpable lesion localization in breast cancer.

BACKGROUND: One-third of all breast cancers are present as clinically nonpalpable lesions. The current gold standard treatment is surgical excision by wire-guided localization. This technique has patient, technical, and scheduling drawbacks. Alternatives exist but depend on radioisotopes with their legislative and waste management issues. Magnetic nanoparticles (MNPs) have already been successfully used for sentinel lymph node biopsy in breast cancer. We therefore aimed to determine the feasibility of using iron oxide MNPs and a handheld magnetometer for the localization of nonpalpable breast cancers using a preclinical model. METHODS: We constructed phantom models to assess the relationship between the handheld magnetometer peak readings and the variation in volume of iron oxide MNPs and their depth of injection in a series of porcine and avian tissue models. We also radiolabeled the MNPs with (99m)Tc and alendronate to create the conjugate (99m)Tc-dipicolylamine-alendronate-MNP and used nano-single-photon emission computed tomography-computed tomography to perform imaging to demonstrate localization properties. RESULTS: The handheld magnetometer readings follow a linear relationship with variations in volume of magnetic tracer and a logarithmic relationship with variations in depth of injection of the magnetic tracer at a fixed volume. The application of derived quadratic equations from the R(2) curves of handheld magnetometer signal versus depth allowed calculation of the depth of injection of iron oxide MNPs from the handheld magnetometer readings and demonstrated the predictable behavior of the iron oxide MNPs and the handheld magnetometer. Satisfactory localization characteristics were confirmed in the phantoms and imaged using nano-single-photon emission computed tomography and computed tomography. CONCLUSIONS: Iron oxide MNPs demonstrate positive localization characteristics in phantom models with predictable behavior patterns. We suggest that the use of MNPs provides a potential technique for the localization of nonpalpable breast lesions and deserves further exploration in animal and human feasibility studies.

The study of etiological and demographic characteristics of neonatal mortality and morbidity - a consecutive case series study from Pakistan.

BACKGROUND: To determine the etiology, management, bacteriological spectrum and outcome of neonatal patients admitted in Civil Hospital Karachi (CHK) and to examine the factors associated with it. METHODS: This hospital based descriptive study of 1463 patients from both sexes who were admitted to Paediatric department, CHK from 1st January 2008 till 31st December 2010 with an established cause according to modified Wigglesworth classification and fulfilling other inclusion criteria were included in the study. Data regarding their demographic profile and potential risk factors was collected on a well structured proforma. Cases were followed until discharge or expiry. Data was analyzed using descriptive statistics. RESULTS: The male to female ratio in our study was 1.12:1. Seven hundred and thirty-four patients were delivered at home (50.2%) and 1010 were less than 7 days old (69%). Out of the total cohort of expired subjects, 89 participants (74.8%) were < 7 days of life. Mortality was more in neonates born at home in rural areas to illiterate mother; 74 patients (62.2%). Most of the deaths; 57 were in neonates suffering from specific infections (47.9%) followed by 38 deaths in immaturity group (31.9%) and 19 related to asphyxial conditions (15.9%). The most common isolates were Staphylococcus aureus (28.7%) followed by Klebsiella (24.8%) and Pseudomonas aeruginosa (16.6 ). One hundred and nineteen (8.13%) of the neonates died in our study group. CONCLUSIONS: These results suggest that neonates with illiterate mothers with high parity and below average socioeconomic level were more susceptible to mortality in the early neonatal period. Most of the cases of mortality were due to specific infections.

The Use of Machine Learning to Reduce Overtreatment of the Axilla in Breast Cancer: Retrospective Cohort Study.

BACKGROUND: Patients with early breast cancer undergoing primary surgery, who have low axillary nodal burden, can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily, following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risks within large patient data sets, but this has not yet been trialed in the arena of axillary node management in breast cancer. OBJECTIVE: The objective of this study was to assess if machine learning techniques could be used to improve preoperative identification of patients with low and high axillary metastatic burden. METHODS: A single-center retrospective analysis was performed on patients with breast cancer who had a preoperative AUS, and the specificity and sensitivity of AUS were calculated. Standard statistical methods and machine learning methods, including artificial neural network, naive Bayes, support vector machine, and random forest, were applied to the data to see if they could improve the accuracy of preoperative AUS to better discern high and low axillary burden. RESULTS: The study included 459 patients; 142 (31%) had a positive AUS; among this group, 88 (62%) had 2 or fewer macrometastatic nodes at ANC. Logistic regression outperformed AUS (specificity 0.950 vs 0.809). Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. CONCLUSIONS: We demonstrated that machine learning improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than 2 metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low axillary burden, and it is unclear whether sentinel node biopsy adds value in this situation. Further studies with larger patient numbers focusing on specific breast cancer subgroups are required to refine these techniques in this setting.