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.

Patient-level costs of staged unilateral versus immediate bilateral symmetrization mammoplasty in breast-conserving surgery.

BACKGROUND: Following therapeutic mammoplasty (TM), the contralateral breast may require a later balancing procedure to optimize shape and symmetry. The alternative is to offer patients simultaneous TM with immediate contralateral symmetrization via a dual-surgeon approach, with the goal of reducing costs and minimizing the number of subsequent hospital appointments in an era of COVID-19 surges. The aim of this cost-consequence analysis is to characterize the cost-benefit of immediate bilateral symmetrization dual-operator mammoplasty versus staged unilateral single operator for breast cancer surgery. METHOD: A prospective single-centre observational study was conducted at an academic teaching centre for breast cancer surgery in the UK. Pseudonymized data for clinicopathological variables and procedural care information, including the type of initial breast-conserving surgery and subsequent reoperation(s), were extracted from the electronic patient record. Financial data were retrieved using the Patient-Level Information and Costing Systems. RESULTS: Between April 2014 and March 2020, 232 women received either immediate bilateral (n = 44), staged unilateral (n = 57) for breast cancer, or unilateral mammoplasty alone (n = 131). The median (interquartile range (i.q.r.)) additional cost of unilateral mammoplasty with staged versus immediate bilateral mammoplasty was €5500 (€4330 to €6570) per patient (P < 0.001), which represents a total supplementary financial burden of €313 462 to the study institution. There was no significant difference between groups in age, Charlson comorbidity index, operating minutes, time to adjuvant radiotherapy in months, or duration of hospital stay. CONCLUSION: Synchronous dual-surgeon immediate bilateral TM can deliver safe immediate symmetrization and is financially beneficial, without delay to receipt of adjuvant therapy, or additional postoperative morbidity.

Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation.

Re-operation due to disease being inadvertently close to the resection margin is a major challenge in breast conserving surgery (BCS). Indocyanine green (ICG) fluorescence imaging could be used to visualize the tumor boundaries and help surgeons resect disease more efficiently. In this work, ICG fluorescence and color images were acquired with a custom-built camera system from 40 patients treated with BCS. Images were acquired from the tumor in-situ, surgical cavity post-excision, freshly excised tumor and histopathology tumour grossing. Fluorescence image intensity and texture were used as individual or combined predictors in both logistic regression (LR) and support vector machine models to predict the tumor extent. ICG fluorescence spectra in formalin-fixed histopathology grossing tumor were acquired and analyzed. Our results showed that ICG remains in the tissue after formalin fixation. Therefore, tissue imaging could be validated in freshly excised and in formalin-fixed grossing tumor. The trained LR model with combined fluorescence intensity (pixel values) and texture (slope of power spectral density curve) identified the tumor's extent in the grossing images with pixel-level resolution and sensitivity, specificity of 0.75 ± 0.3, 0.89 ± 0.2.This model was applied on tumor in-situ and surgical cavity (post-excision) images to predict tumor presence.

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study.

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research.

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.

Assessment of Technical Skills in Axillary Lymph Node Dissection.

OBJECTIVE: A simulator to enable safe practice and assessment of ALND has been designed, and face, content and construct validity has been investigated. SUMMARY AND BACKGROUND DATA: The reduction in the number of ALNDs conducted has led to decreased resident exposure and confidence. METHODS: A cross-sectional multicenter observational study was carried out between July 2017 and August 2018. Following model development, 30 surgeons of varying experience (n = "experts," n = 11 "senior residents," and n = 10 "junior residents") were asked to perform a simulated ALND. Face and content validity questionnaires were administered immediately after ALND. All ALND procedures were retrospectively assessed by 2 attending breast surgeons, blinded to operator identity, using a video-based assessment tool, and an end product assessment tool. RESULTS: Statistically significant differences between groups were observed across all operative subphases on the axillary clearance assessment tool (P < 0.001). Significant differences between groups were observed for overall procedure quality (P < 0.05) and total number of lymph nodes harvested (P < 0.001). However, operator grade could not be distinguished across other end product variables such as axillary vein damage (P = 0.864) and long thoracic nerve injury (P = 0.094). Overall, participants indicated that the simulator has good anatomical (median score >7) and procedural realism (median score >7). CONCLUSIONS: Video-based analysis demonstrates construct validity for ALND assessment. Given reduced ALND exposure, this simulation is a useful adjunct for both technical skills training and formative Deanery or Faculty administered assessments.

The Impact of Temporal Variation in Indocyanine Green Administration on Tumor Identification During Fluorescence Guided Breast Surgery.

BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.

De-epithelialized Skin Flaps to Minimize Complications in Large Breast Reconstruction: A Tailored Approach.

ABSTRACT: Mastectomy and immediate reconstruction may be challenging in patients with large breasts, especially when significant ptosis is also present. Skin-reducing mastectomy (SRM) is usually indicated in these cases, although with increased morbidity. The aims of the study were to introduce 2 modifications of the classic technique and to incorporate them in the management algorithm to improve the outcomes.Twenty patients fulfilling the criteria for SRM underwent mastectomy and reconstruction either with the "classic SRM" (8 patients) or with 1 of the 2 modifications described here: modification A "vertical limb bridging" (for patients with very large breasts, 2 patients) and modification B "dual coverage" (for patients with moderate breasts, 10 patients). All reconstructions were performed using a slow progressive expansion of the implant. Herein, we describe the techniques along with the proposed indications for each one of them.There was no reconstruction failure, and all patients were satisfied with the final results. There were 2 cases with T junction, lateral skin flap partial ischemia managed with delayed revision of the wound on the fifth postoperative day to allow less skin excision. One patient (smoker) developed severe lower pole cellulitis, which was managed conservatively. Finally, 1 patient who underwent radiotherapy developed a late infected seroma, which was managed successfully with drainage and antibiotics. Overall, there was good lower pole projection even with the dual-coverage modification.Skin-reducing mastectomy can be tailored according to individual patient anatomy, and the high reported complication rate associated with this technique can be minimized using certain surgical modifications, tissue expanders with progressive inflation, and good patient selection.

The Modified Crescenteric Anterior Intercostal Perforator Flap.

Lower pole breast cancers are challenging to manage because conventional wide local excision may produce a "bird's beak" deformity. In an era of oncoplastic surgery, techniques that balance oncological results with cosmetic outcomes such as local flaps have extended the role of breast-conserving surgery. Local flaps are particularly useful for partial breast reconstruction due to the relative simplicity of the surgical procedure and reduced morbidity. Intercostal artery perforator flaps have a shorter duration of surgery than free flaps and do not require microsurgical anastomoses. Anterior intercostal artery perforator (AICAP) flaps provide excellent cosmesis, yet traditional crescenteric harvest yields limited volume for reconstruction. We describe a modification to an established reconstructive technique for lower pole breast defects. The technique is based on 3 extensions of tissue, providing a larger volume of tissue replacement compared with traditional AICAP flaps. The technique is particularly suitable for small- and medium-sized non-ptotic breasts, with lower pole tumors. The modified crescenteric AICAP technique can be used to increase the available tissue when performing lower pole reconstructions.

The feasibility and safety of immediate breast reconstruction in the COVID-19 era.

The coronavirus disease-2019 pandemic has had a significant impact on the delivery of surgical services, particularly reconstructive surgery. This article examines the current evidence to assess the feasibility of recommencing immediate breast reconstruction services during the pandemic and highlights considerations required to ensure patient safety.

Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.

INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound. METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy. RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%. CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients with PND.

Enhancer mapping uncovers phenotypic heterogeneity and evolution in patients with luminal breast cancer.

The degree of intrinsic and interpatient phenotypic heterogeneity and its role in tumor evolution is poorly understood. Phenotypic drifts can be transmitted via inheritable transcriptional programs. Cell-type specific transcription is maintained through the activation of epigenetically defined regulatory regions including promoters and enhancers. Here we have annotated the epigenome of 47 primary and metastatic estrogen-receptor (ERα)-positive breast cancer clinical specimens and inferred phenotypic heterogeneity from the regulatory landscape, identifying key regulatory elements commonly shared across patients. Shared regions contain a unique set of regulatory information including the motif for transcription factor YY1. We identify YY1 as a critical determinant of ERα transcriptional activity promoting tumor growth in most luminal patients. YY1 also contributes to the expression of genes mediating resistance to endocrine treatment. Finally, we used H3K27ac levels at active enhancer elements as a surrogate of intra-tumor phenotypic heterogeneity to track the expansion and contraction of phenotypic subpopulations throughout breast cancer progression. By tracking the clonality of SLC9A3R1-positive cells, a bona fide YY1-ERα-regulated gene, we show that endocrine therapies select for phenotypic clones under-represented at diagnosis. Collectively, our data show that epigenetic mechanisms significantly contribute to phenotypic heterogeneity and evolution in systemically treated breast cancer patients.

Streamlining Decision Making in Contralateral Risk-Reducing Mastectomy: Impact of PREDICT and BOADICEA Computations.

INTRODUCTION: Patients with sporadic breast cancer (BC) have low contralateral breast cancer risk (CLBCR; approximately 0.7% per annum) and contralateral prophylactic mastectomy (CPM) offers no survival advantage. CPM with autologous reconstruction (AR) has major morbidity and resource implications. OBJECTIVE: The aim of this study was to review the impact of PREDICT survival estimates and lifetime CLBCR scores on decision making for CPM in patients with unilateral BC. METHODS: Of n = 272 consecutive patients undergoing mastectomy and AR, 252 were included. Five- and 10-year survival was computed with the PREDICT(V2) online prognostication tool, using age and clinicopathological factors. Based on family history (FH) and tumor biology, CLBCR was calculated using validated BODICEA web-based software. Survival scores were correlated against CLBCR estimates to identify patients receiving CPM with 'low' CLBCR (< 30% lifetime risk) and poor prognosis (5-year survival < 80%). Patients with 'high' CLBCR receiving unilateral mastectomy (UM) were similarly identified (UK National Institute of Health and Care Excellence [NICE] criteria for CPM, ≥ 30% lifetime BC risk). Justifications motivating CPM were investigated. RESULTS: Of 252 patients, 215 had UM and 37 had bilateral mastectomy and AR. Only 23 (62%) patients receiving CPM fulfilled the NICE criteria. Of 215 patients, 5 (2.3%) failed to undergo CPM despite high CLBCR and good prognosis. CPMs were performed, at the patient's request, for no clear justification (n = 8), contralateral non-invasive disease, and/or FH (n = 5), FH alone (n = 4) and ipsilateral cancer recurrence-related anxiety (n = 3). CONCLUSION: In the absence of prospective risk estimates of CLBCR and prognosis, certain patients receive CPM and reconstruction despite modest CLBCR, yet a proportion of patients with good prognoses and substantial risk are not undergoing CPM.

IPET study: an FLT-PET window study to assess the activity of the steroid sulfatase inhibitor irosustat in early breast cancer.

BACKGROUND: Steroid sulfatase (STS) is involved in oestrogen biosynthesis and irosustat is a first generation, irreversible steroid sulfatase inhibitor. A pre-surgical window-of-opportunity study with irosustat was undertaken in estrogen receptor-positive (ER+) breast cancer to assess the effect of irosustat on tumour cell proliferation as measured by 3'-deoxy-3'-[18F] fluorothymidine uptake measured by PET scanning (FLT-PET) and Ki67. METHODS: Postmenopausal women with untreated ER+ early breast cancer were recruited, and imaged with FLT-PET at baseline and after at least 2 weeks treatment with irosustat, 40 mg once daily orally. The primary endpoint was changed in FLT uptake; secondary endpoints included safety and tolerability of irosustat, changes in tumoral Ki67 and steroidogenic enzymes expression and circulating steroid hormone levels. RESULTS: Thirteen women were recruited, and ten started irosustat for 2 weeks, followed by repeat FLT-PET scans in eight. Defining response as decreases of ≥20% in standardized uptake value (SUV) or ≥30% in Ki, 1 (12.5% (95% CI 2-47%, p = 0.001)) and 3 (43% (95% CI 16-75%, p = <0.001) patients, respectively, responded. 6 out of 7 patients had a Ki67 reduction (range = -19.3 to 76.4%), and median percentage difference in Ki67 was 52.3% (p = 0.028). In one patient with a low baseline STS expression, a 19.7% increase in Ki67 was recorded. STS decreases were seen in tumours with high basal STS expression, significant decreases were also noted in aromatase, and 17ß-hydroxysteroid dehydrogenase type 1 and 2. Irosustat was generally well tolerated with all adverse event CTCAE Grade ≤2. CONCLUSIONS: Irosustat resulted in a significant reduction in FLT uptake and Ki67, and is well tolerated. These data are the first demonstrating clinical activity of irosustat in early breast cancer. Baseline expression of STS may be a biomarker of sensitivity to irosustat.

Diagnostic Accuracy of Intraoperative Techniques for Margin Assessment in Breast Cancer Surgery: A Meta-analysis.

OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis to clarify the diagnostic accuracy of intraoperative breast margin assessment (IMA) techniques against which the performance of emerging IMA technologies may be compared. SUMMARY OF BACKGROUND DATA: IMA techniques have failed to penetrate routine practice due to limitations, including slow reporting times, technical demands, and logistics. Emerging IMA technologies are being developed to reduce positive margin and re-excision rates and will be compared with the diagnostic accuracy of existing techniques. METHOD: Studies were identified using electronic bibliographic searches up to January 2016. MESH terms and all-field search terms included "Breast Cancer" AND "Intraoperative" AND "Margin." Only clinical studies with raw diagnostic accuracy data as compared with final permanent section histopathology were included. A bivariate model for diagnostic meta-analysis was used to attain overall pooled sensitivity and specificity. RESULTS: Eight hundred thirty-eight unique studies revealed 35 studies for meta-analysis. Pooled sensitivity (Sens), specificity (Spec), and area under the receiver operating characteristic curve (AUROC) values were calculated per group (Sens, Spec, AUROC): frozen section = 86%, 96%, 0.96 (n = 9); cytology = 91%, 95%, 0.98 (n = 11); intraoperative ultrasound = 59%, 81%, 0.78 (n = 4); specimen radiography = 53%, 84%, 0.73 (n = 9); optical spectroscopy = 85%, 87%, 0.88 (n = 3). CONCLUSIONS: Pooled data suggest that frozen section and cytology have the greatest diagnostic accuracy. However, these methods are resource intensive and turnaround times for results have prevented widespread international adoption. Emerging technologies need to compete with the diagnostic accuracy of existing techniques while offering advantages in terms of speed, cost, and reliability.

Trends in Immediate Postmastectomy Breast Reconstruction in the United Kingdom.

BACKGROUND: The study aimed to evaluate local and national trends in immediate breast reconstruction (IBR) using the national English administrative records, Hospital Episode Statistics. Our prediction was an increase in implant-only and free flap procedures and a decline in latissimus flap reconstructions. METHODS: Data from an oncoplastic center were interrogated to derive numbers of implant-only, autologous latissimus dorsi (LD), LD-assisted, and autologous pedicled or free flap IBR procedures performed between 2004 and 2013. Similarly, Hospital Episode Statistics data were used to quantify national trends in these procedures from 1996 to 2012 using a curve fitting analysis. RESULTS: National data suggest an increase in LD procedures between 1996 (n = 250) and 2002 (n = 958), a gradual rise until 2008 (n = 1398) followed by a decline until 2012 (n = 1090). As a percentage of total IBR, trends in LD flap reconstruction better fit a quadratic (R(2) = 0.97) than a linear function (R(2) = 0.63), confirming a proportional recent decline in LD flap procedures. Conversely, autologous (non-LD) flap reconstructions have increased (1996 = 0.44%; 2012 = 2.76%), whereas implant-only reconstructions have declined (1996 = 95.42%; 2012 = 84.92%). Locally, 70 implant-assisted LD procedures were performed in 2003 -2004, but only 2 were performed in 2012 to 2013. CONCLUSIONS: Implants are the most common IBR technique; autologous free flap procedures have increased, and pedicled LD flap procedures are in decline.

Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning.

Current techniques for assessing the adequacy of tumour excision during breast conserving surgery do not provide real-time direct cytopathological assessment of the internal cavity walls within the breast. This study investigates the ability of probe-based confocal laser endomicroscopy (pCLE), an emerging imaging tool, to image the morphology of neoplastic and non-neoplastic breast tissues, and determines the ability of histopathologists and surgeons to differentiate these images. Freshly excised tumour samples and adjacent non-diseased sections from 50 consenting patients were stained with 0.01 % acriflavine hydrochloride and imaged using pCLE. All discernible pCLE features were cross-examined with conventional histopathology. Following pattern recognition training, 17 histopathologists and surgeons with no pCLE experience interpreted 50 pCLE images independently whilst blinded to histopathology results. Three-hundred and fifty pCLE image mosaics were analysed. Consistent with histopathology findings, the glandular structures, adipocytes and collagen fibres of normal breast were readily visible on pCLE images. These were distinguishable from the morphological architecture exhibited by invasive and non-invasive carcinoma. The mean accuracy of pCLE image interpretation for histopathologists and surgeons was 94 and 92 %, respectively. Overall, inter-observer agreement for histopathologists was 'almost perfect', κ = 0.82; and 'substantial' for surgeons, κ = 0.74. pCLE morphological features of neoplastic and non-neoplastic breast tissues are readily visualized and distinguishable with high accuracy by both histopathologists and surgeons. Further research is required to investigate a potential role for the use of pCLE intraoperatively for in situ detection of residual cancerous foci, thereby guiding operating decision-making based on real-time breast cavity scanning.

Systemic inflammatory response syndrome in a patient diagnosed with high grade inflammatory triple negative breast cancer: a case report of a potentially rare paraneoplastic syndrome.

BACKGROUND: Inflammatory breast cancer is a complex pathological entity associated with poor outcomes. This loco-regional disease is characterised by a rapid clinical course in the presence breast erythema and infiltration of dermal lymphatics by tumours cells. Herein we describe a case of inflammatory breast cancer with a rare presentation and disease course defined by a profound systemic inflammatory response in the absence of an infective cause. CASE PRESENTATION: The patient presented with pyrexia and malaise following a recent tissue diagnosis of inflammatory breast cancer. At the time of admission the patient demonstrated clinical features of the systemic inflammatory response syndrome (SIRS) in the presence of a negative septic screen. Her condition deteriorated despite systemic broad spectrum intravenous antibiotics and she underwent surgical debulking of a 180 × 135 × 100 mm (821 g) primary tumour composed of oedematous, friable and haemorrhagic tissue (pT4,N1a,M0; oestrogen/progesterone/HER-2 receptor negative). Following surgery, the clinical picture dramatically improved with cessation of SIRS and normalisation of inflammatory markers. After 4 weeks the patient required readmission to hospital due to recurrent SIRS and negative septic screen. The patient received treatment with systemic chemotherapy showing transient clinical improvement and suppression of SIRS. Despite on going chemotherapy, systemic antibiotics and a trial of steroid therapy the patient died 5 months after her initial presentation to hospital. At the time of death she demonstrated persistent SIRS with elevated inflammatory markers. CONCLUSION: This is the first case report of inflammatory breath cancer associated with SIRS in the absence of clinically confirmed infection. Important learning points highlighted by this case are: (a) recognition of the diagnostic and therapeutic uncertainties that still exist in the context of inflammatory breast cancer; (b) appreciation of the potential paraneoplastic systemic inflammatory manifestations of this disease, and finally; (c) the importance a multidisciplinary and multimodal approach to treatment.

Surgical treatment of primary hyperparathyroidism: description of techniques and advances in the field.

Primary hyperparathyroidism is a disease commonly seen in patients above 60 years of age. It is the most common cause of asymptomatic or symptomatic hypercalcemia, usually found incidentally on routine check-ups. Surgical treatment is the only definitive treatment of choice in the symptomatic patient; however, it can also be employed in asymptomatic patients. First described in 1925, bilateral neck exploration is the gold standard of treatment for primary hyperparathyroidism. The recent interest in minimally invasive surgeries has led to better and improved techniques of neck exploration with improved cosmetic results and lesser chances of transient or permanent hypoparathyroidism due to inadvertent removal of normally functioning parathyroid tissue. These include unilateral neck explorations, minimally invasive parathyroidectomies and minimally invasive radio-guided parathyroidectomy. The intact parathyroid hormone assays have greatly added to the detection of normal and abnormal functioning glands, hence better surgical outcomes.

Diagnostic accuracy of tactile imaging in selecting patients with palpable breast abnormalities: a prospective comparative study.

Unnecessary referrals of patients with breast lumps represent a significant issue, since only a few patients actually have lumps when examined by a breast specialist. Tactile imaging (TI) is a novel modality in breast diagnostics armamentarium. The aim of this study was to assess TI's diagnostic performance and compare it to clinical breast examination (CBE). This is a prospective, blinded, comparative study of 276 consecutive patients. All patients underwent conventional imaging and tissue sampling if either a radiological or a palpable abnormality was present. Sensitivity, specificity and positive and negative predictive values for CBE and TI were calculated. Radiological findings and final diagnosis based on histology and/or cytology were used as reference standards. Receiver operator characteristic (ROC) curve analysis was also performed for each method. Sensitivity and specificity of TI in detecting radiologically proven abnormalities were 85.5 % and 35 %, respectively. CBE's sensitivity was 80.3 % and specificity 76 %. In detecting a histopathological entity according to histology/cytology, sensitivity was 88.2 % for TI and 81.6 % for CBE. Specificity was 38.5 % and 85.7 % for TI and CBE, respectively. These results suggest a trend towards higher sensitivity of TI compared to CBE but significantly lower specificity. Subgroup analysis revealed superior sensitivity of TI in detecting a histological entity in pre-menopausal women. However, CBE's overall performance was superior compared to TI's according to ROC curve analysis. Although further research is necessary, the use of TI by the primary care physician as a selection tool for referring patients to a breast specialist should be considered especially in pre-menopausal women.