Is blue dye still required during sentinel lymph node biopsy for breast cancer?

BACKGROUND: In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates. METHODS: Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique. RESULTS: A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% (n = 158/160), with blue dye alone 92.5% (n = 148/160) and with radioisotope alone 97.5% (n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients. CONCLUSION: The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation

Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography.

Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment

Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy.

ObjectivesTo examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy.DesignOpen-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study.MethodsHIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms.ResultsAll eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046).ConclusionSBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy

High intensity focused ultrasound in the treatment of breast fibroadenomata (HIFU-F trial)

Background: High intensity focused ultrasound (HIFU) is a non-invasive ablative technique utilising the application of high frequency ultrasound (US) pressure waves to cause tissue necrosis. This emerging technology is currently limited by prolonged treatment times. The aim of the HIFU-F trial was to perform circumferential HIFU treatment as a means of shortening treatment times. Methods: A prospective trial was set up to treat 50 consecutive patients ≥18 years of age. Eligible patients possessed symptomatic fibroadenomata, visible on US. Patients ≥25 years of age required histological confirmation of the diagnosis. Primary outcome measures were reduction in treatment time, reduction in volume on US after 12 months and complication rates. Results: HIFU treatment was performed in 51 patients (53 treatments) with a mean age of 29.8 years (SD 7.2 years) and diameter of 2.6 cm (SD 1.4 cm). Circumferential ablation reduced treatment times by an estimated 19.9 minutes (SD 25.1 minutes), which is a 29.4% (SD 15.2%) reduction compared to whole lesion ablation. Volume reduction of 43.2% (SD 35.4%; p<0.005, paired t-test) was observed on US at 12 months post-treatment. Local complications completely resolved at one month apart from skin hyper-pigmentation, which persisted in nine cases at three months, six cases at six months and six at 12 months. Conclusion: Circumferential HIFU treatment for breast fibroadenomata is feasible to reduce both lesion size and treatment time. HIFU is a non-invasive alternative technique for the treatment of breast fibroadenomata

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"?

With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion

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 60 min. 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. Graphical abstract Variable volumes and concentrations of a magnetic tracer were injected into the third inguinal mammary gland bilaterally in an in vivo porcine model (1) allowing the performance of magnetic sentinel lymph node biopsy of draining inguinal nodes (2). The harvested nodes were ‘darkly stained’ for iron uptake and ‘hot’ for magnetometer counts (3). The iron was deposited within the cortex and subcapsular space – visible as blue using PERL’s staining – on histopathology (4) and was quantified using quantitative magnetometry and a validated iron-grading scale

Systematic review of high-intensity focused ultrasound ablation in the treatment of breast cancer

Background A systematic review was undertaken to assess the clinical efficacy of non-invasive high-intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer. Methods MEDLINE/PubMed library databases were used to identify all studies published up to December 2013 that evaluated the role of HIFU ablation in the treatment of breast cancer. Studies were eligible if they were performed on patients with breast cancer and objectively recorded at least one clinical outcome measure of response (imaging, histopathological or cosmetic) to HIFU treatment. Results Nine studies fulfilled the inclusion criteria. The absence of tumour or residual tumour after treatment was reported for 95·8 per cent of patients (160 of 167). No residual tumour was found in 46·2 per cent (55 of 119; range 17-100 per cent), less than 10 per cent residual tumour in 29·4 per cent (35 of 119; range 0-53 per cent), and between 10 and 90 per cent residual tumour in 22·7 per cent (27 of 119; range 0-60 per cent). The most common complication associated with HIFU ablation was pain (40·1 per cent) and less frequently oedema (16·8 per cent), skin burn (4·2 per cent) and pectoralis major injury (3·6 per cent). MRI showed an absence of contrast enhancement after treatment in 82 per cent of patients (31 of 38; range 50-100 per cent), indicative of coagulative necrosis. Correlation of contrast enhancement on pretreatment and post-treatment MRI successfully predicted the presence of residual disease. Conclusion HIFU treatment can induce coagulative necrosis in breast cancers. Complete ablation has not been reported consistently on histopathology and no imaging modality has been able confidently to predict the percentage of complete ablation. Consistent tumour and margin necrosis with reliable follow-up imaging are required before HIFU ablation can be evaluated within large, prospective clinical trials. Many questions remai