Clinicopathological Predictors of Positive Resection Margins in Breast-Conserving Surgery.

BACKGROUND: Ductal carcinoma in situ (DCIS) is associated with risk of positive resection margins following breast-conserving surgery (BCS) and subsequent reoperation. Prior reports grossly underestimate the risk of margin positivity with IBC containing a DCIS component (IBC + DCIS) due to patient-level rather than margin-level analysis. OBJECTIVE: The aim of this study was to delineate the relative risk of IBC + DCIS compared with pure IBC (without a DCIS component) on margin positivity through detailed margin-level interrogation. METHODS: A single institution, retrospective, observational cohort study was conducted in which pathology databases were evaluated to identify patients who underwent BCS over 5 years (2014-2019). Margin-level interrogation included granular detail into the extent, pathological subtype and grade of disease at each resection margin. Predictors of a positive margin were computed using multivariate regression analysis. RESULTS: Clinicopathological details were examined from 5454 margins from 909 women. The relative risk of a positive margin with IBC + DCIS versus pure IBC was 8.76 (95% confidence interval [CI] 6.64-11.56) applying UK Association of Breast Surgery guidelines, and 8.44 (95% CI 6.57-10.84) applying the Society of Surgical Oncology/American Society for Radiation Oncology guidelines. Independent predictors of margin positivity included younger patient age (0.033, 95% CI 0.006-0.060), lower specimen weight (0.045, 95% CI 0.020-0.069), multifocality (0.256, 95% CI 0.137-0.376), lymphovascular invasion (0.138, 95% CI 0.068-0.208) and comedonecrosis (0.113, 95% CI 0.040-0.185). CONCLUSIONS: Compared with pure IBC, the relative risk of a positive margin with IBC + DCIS is approximately ninefold, significantly higher than prior estimates. This margin-level methodology is believed to represent the impact of DCIS more accurately on margin positivity in IBC.

Nipple aspirate fluid and its use for the early detection of breast cancer.

Nipple aspirate fluid is the physiological biofluid lining ductal epithelial cells. Historically, cytology of nipple fluid has been the gold standard diagnostic method for assessment of ductal fluid in patients with symptomatic nipple discharge. The role of biomarker discovery in nipple aspirate fluid for assessment of asymptomatic and high-risk patients is highly attractive but evaluation to date is limited by poor diagnostic accuracy. However, the emergence of new technologies capable of identifying metabolites that have been previously thought unidentifiable within such small volumes of fluid, has enabled testing of nipple biofluid to be re-examined. This review evaluates the use of new technologies to evaluate the components of nipple fluid and their potential to serve as biomarkers in screening.

Diagnostic Accuracy of Nipple Discharge Fluid Cytology: A Meta-Analysis and Systematic Review of the Literature.

BACKGROUND: Nipple discharge is the third most frequent complaint of women attending rapid diagnostic breast clinics. Nipple smear cytology remains the single most used diagnostic method for investigating fluid content. This study aimed to conduct a systematic review and meta-analysis of the diagnostic accuracy of nipple discharge fluid assessment. METHODS: The study incorporated searches for studies interrogating the diagnostic data of nipple discharge fluid cytology compared with the histopathology gold standard. Data from studies published from 1956 to 2019 were analyzed. The analysis included 8648 cytology samples of women with a presenting complaint of nipple discharge. Both hierarchical and bivariate models for diagnostic meta-analysis were used to attain overall pooled sensitivity and specificity. RESULTS: Of 837 studies retrieved, 45 fulfilled the criteria for inclusion. The diagnostic accuracy of the meta-analysis examining nipple discharge fluid had a sensitivity of 75 % (95 % confidence interval [CI], 0.74-0.77) and a specificity of 87 % (95 % CI, 0.86-0.87) for benign breast disease. For breast cancer, it had a sensitivity of 62 % (95 % CI, 0.53-0.71) and a specificity 71 % (95 % CI, 0.57-0.81). Furthermore, patients presenting with blood-stained discharge yielded an overall malignancy rate of 58 % (95 % CI, 0.54-0.60) with a positive predictive value (PPV) of 27 % (95 % CI, 0.17-0.36). CONCLUSIONS: Pooled data from studies encompassing nipple discharge fluid assessment suggest that nipple smear cytology is of limited diagnostic accuracy. The authors recommend that a tailored approach to diagnosis be required given the variable sensitivities of currently available tests.

Breast health screening: a UK-wide questionnaire.

BACKGROUND: Currently, there is an unmet clinical need in identifying and screening women at high risk of breast cancer, where tumours are often aggressive and treatment intervention is too late to prevent metastasis, recurrence and mortality. This has been brought into sharp focus by the SARS-CoV-2 global pandemic, constantly changing hospital policies and surgical guidelines in reducing access to established screening and treatment regimens. Nipple aspirate fluid (NAF), is thought to provide a unique window into the biological processes occurring within the breast, particularly in the context of a developing neoplasm. Evaluation of NAF in asymptomatic women, for novel chemical biomarkers of either early disease and/or cancer risk offers tremendous promise as a tool to facilitate early detection and to supplement screening. However, it is acceptability as a method of collection and screening by women is critical and yet unknown. A breast health questionnaire was disseminated to women through breast cancer charities, patient support groups and social media platforms, with the aim of collecting opinions on the acceptability of use of NAF as a potential screening tool. METHOD: Following ethical approval a questionnaire was prepared using online surveys consisting of four parts: (a) introduction on breast health screening in the UK, (b) core demographic data, (c) questions regarding screening and the acceptability of using NAF and (d) opinions about the process of collecting and using nipple fluid for screening. The voluntary and anonymous questionnaire was disseminated through social media, professional networks, charity websites and by individuals between October 2019 and December 2020. Survey responses were collected electronically, and the data analysed using online surveys statistical tools. RESULTS: A total of 3178 women completed the questionnaire (65.9% Caucasian, 27.7% Asian/British Asian, 0.6% black and 5.0% other). Of these, 2650 women (83.4%) had no prior knowledge of NAF and 89.4% were unaware that NAF can be expressed in up to 90% of all women. Concerning their risk of breast cancer, 89.8% of women were keen to know their future risk of breast cancer, 8.5% were unsure whether they wanted to know their risk and a further, 1.6% did not want to know. Regarding screening, 944 women (29.8%) were unaware of the lack of routine National Health Service Breast Screening for those under the age of 47 years. Furthermore, 53.0% of women were unaware that mammographic screening is affected by breast density. In terms of the acceptability of home testing for breast health, 92.0% were keen to undergo a home test. Both 79.7% and 70.9% stated they would consider hand massage and a breast pump to acquire nipple fluid samples, respectively. A further 48.6% of women would consider the use of a hormonal nasal spray for the same purpose. However, with regards to acquiring results from NAF testing, 42.6% of women would prefer to receive results at home and 34.2% in a medical facility. Finally, 91.6% of women believed that breast health should be incorporated as part of school education curriculum. CONCLUSION: Public awareness regarding breast screening protocols and limitations of mammography could be improved. Many women were unaware that NAF might be a useful biofluid for future risk prediction, and yet the concept of self-testing of nipple fluid, with either hand massage or a breast pump was well received. Efforts should be made to increase awareness of the benefits of alternative and supplementary tests, especially in the context of high-risk individuals and younger patients.

Diagnostic Accuracy of Nipple Aspirate Fluid Cytology in Asymptomatic Patients: A Meta-analysis and Systematic Review of the Literature.

PURPOSE: To calculate the diagnostic accuracy of nipple aspirate fluid (NAF) cytology. BACKGROUND: Evaluation of NAF cytology in asymptomatic patients conceptually offers a non-invasive method for either screening for breast cancer or else predicting or stratifying future cancer risk. METHODS: Studies were identified by performing electronic searches up to August 2019. A meta-analysis was conducted to attain an overall pooled sensitivity and specificity of NAF for breast cancer detection. RESULTS: A search through 938 studies yielded a total of 19 studies. Overall, 9308 patients were examined, with cytology results from 10,147 breasts [age (years), mean ± SD = 49.73 ± 4.09 years]. Diagnostic accuracy meta-analysis of NAF revealed a pooled specificity of 0.97 (95% CI 0.97-0.98), and sensitivity of 0.64 (95% CI 0.62-0.66). CONCLUSIONS: The diagnostic accuracy of nipple smear cytology is limited by poor sensitivity. If nipple fluid assessment is to be used for diagnosis, then emerging technologies for fluid biomarker analysis must supersede the current diagnostic accuracy of NAF cytology.

Meta-analysis Comparing Fluorescence Imaging with Radioisotope and Blue Dye-Guided Sentinel Node Identification for Breast Cancer Surgery.

INTRODUCTION: Conventional methods for axillary sentinel lymph node biopsy (SLNB) are fraught with complications such as allergic reactions, skin tattooing, radiation, and limitations on infrastructure. A novel technique has been developed for lymphatic mapping utilizing fluorescence imaging. This meta-analysis aims to compare the gold standard blue dye and radioisotope (BD-RI) technique with fluorescence-guided SLNB using indocyanine green (ICG). METHODS: This study was registered with PROSPERO (CRD42019129224). The MEDLINE, EMBASE, Scopus, and Web of Science databases were searched using the Medical Subject Heading (MESH) terms 'Surgery' AND 'Lymph node' AND 'Near infrared fluorescence' AND 'Indocyanine green'. Studies containing raw data on the sentinel node identification rate in breast cancer surgery were included. A heterogeneity test (using Cochran's Q) determined the use of fixed- or random-effects models for pooled odds ratios (OR). RESULTS: Overall, 1748 studies were screened, of which 10 met the inclusion criteria for meta-analysis. ICG was equivalent to radioisotope (RI) at sentinel node identification (OR 2.58, 95% confidence interval [CI] 0.35-19.08, p < 0.05) but superior to blue dye (BD) (OR 9.07, 95% CI 6.73-12.23, p < 0.05). Furthermore, ICG was superior to the gold standard BD-RI technique (OR 4.22, 95% CI 2.17-8.20, p < 0.001). CONCLUSION: Fluorescence imaging for axillary sentinel node identification with ICG is equivalent to the single technique using RI, and superior to the dual technique (RI-BD) and single technique with BD. Hospitals using RI and/or BD could consider changing their practice to ICG given the comparable efficacy and improved safety profile, as well as the lesser burden on hospital infrastructure.

The effects of pre-operative intra-articular glenohumeral corticosteroid injection on infective complications after shoulder arthroplasty.

BACKGROUND: Many shoulder surgeons use intra-articular corticosteroid injections (IACI) in shoulder osteoarthritis, with the caveat that it precludes arthroplasty for at least 6 months to 12 months because of the theoretical risk of infection. To our knowledge, there is nothing available in the literature to support this notion. METHODS: We undertook a retrospective, matched cohort study of all patients who underwent shoulder arthroplasty in our unit between December 2010 and December 2013 aiming to assess whether pre-operative IACI had an impact on infective complications. Group I had received an IACI prior to their arthroplasty and Group II had not. A chi-squared analysis was performed (p < 0.05). RESULTS: Group I comprised 23 patients with a mean age of 73 years (range 54 years to 90 years) had 23 shoulder arthroplasties and had mean follow-up of 16.6 months. Patients received an IACI approximately 11.4 months (range 2.5 months to 172.5 months) before their surgery. One patient developed a deep joint infection that warranted revision arthroplasty. Group II comprised 60 patients with a mean age of 75 years (range 34 years to 90 years) had 64 shoulder arthoplasties and a mean follow-up of 20.1 months. No patients developed infective complications (p > 0.05), implying there was no statistically significant relationship between pre-operative IACI and infective complications. CONCLUSIONS: We could not establish a causal link between IACI and infective complications after arthoplasty.

Nasu-hakola syndrome: an unusual cause of pathological fractures.

Nasu-Hakola syndrome is a hereditary cause of pathological fractures. Uniquely, patients also develop neuropsychiatric symptoms and signs. The disease is ultimately fatal. We propose a management strategy for pathological fractures in sufferers based on the stage of the disease.

Bilateral atypical insufficiency fractures of the proximal tibia and a unilateral distal femoral fracture associated with long-term intravenous bisphosphonate therapy: a case report.

INTRODUCTION: Atypical insufficiency fractures of the femur in patients on long-term bisphosphonate therapy have been well described in recent literature. The majority of cases are associated with minimal or no trauma and occur in the subtrochanteric or diaphyseal region. CASE PRESENTATION: We describe the case of a 76-year-old British Caucasian woman who presented initially to an emergency department and then to her primary care physician with a long-standing history of bilateral knee pain after minor trauma. Plain radiographs showed subtle linear areas of sclerosis bilaterally in her proximal tibiae. Magnetic resonance imaging confirmed the presence of insufficiency fractures in these areas along with her left distal femur. There are very few reports of atypical insufficiency fractures involving the tibia in patients on long-term bisphosphonate therapy and this appears to be the only documented bilateral case involving the metaphyseal regions of the proximal tibia and distal femur. CONCLUSION: In addition to existing literature describing atypical fractures in the proximal femur and femoral shaft, there is a need for increased awareness that these fractures can also occur in other weight-bearing areas of the skeleton. All clinicians involved in the care of patients taking long-term bisphosphonates need to be aware of the growing association between new onset lower limb pain and atypical insufficiency fractures.