Barry, P., Vatsiou, A., Spiteri, I., Nichol, D., Cresswell, G.D., Acar, A., Trahearn, N., Hrebien, S., Garcia-Murillas, I., Chkhaidze, K., et al.
(2018). The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer. Clin cancer res,
Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors.Experimental Design: In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing (n = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA).Results: Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. Clin Cancer Res; 24(19); 4763-70. ©2018 AACR..
O'Connell, R.L., Khabra, K., Bamber, J.C., deSouza, N., Meybodi, F., Barry, P.A. & Rusby, J.E.
(2018). Validation of the Vectra XT three-dimensional imaging system for measuring breast volume and symmetry following oncological reconstruction. Breast cancer res treat,
PURPOSE: Three-dimensional surface imaging (3D-SI) of the breasts enables the measurement of breast volume and shape symmetry. If these measurements were sufficiently accurate and repeatable, they could be used in planning oncological breast surgery and as an objective measure of aesthetic outcome. The aim of this study was to validate the measurements of breast volume and symmetry provided by the Vectra XT imaging system. METHODS: To validate measurements, breast phantom models of true volume between 100 and 1000 cm3 were constructed and varying amounts removed to mimic breast tissue 'resections'. The volumes of the phantoms were measured using 3D-SI by two observers and compared to a gold standard. For intra-observer repeatability and inter-observer reproducibility in vivo, 16 patients who had undergone oncological breast surgery had breast volume and symmetry measured three times by two observers. RESULTS: A mean relative difference of 2.17 and 2.28% for observer 1 and 2 respectively was seen in the phantom measurements compared to the gold standard (n = 45, Bland Altman agreement). Intra-observer variation over ten repeated measurements demonstrated mean coefficients of variation (CV) of 0.58 and 0.49%, respectively. The inter-observer variation demonstrated a mean relative difference of 0.11% between the two observers. In patients, intra-observer variation over three repeated volume measurements for each observer was 3.9 and 3.8% (mean CV); the mean relative difference between observers was 5.78%. For three repeated shape symmetry measurements using RMS projection difference between the two breasts, the intra-observer variations were 8 and 14% (mean CV), the mean relative difference between observers was 0.43 mm for average symmetry values that ranged from about 3.5 to 15.5 mm. CONCLUSION: This first validation of breast volume and shape symmetry measurements using the Vectra XT 3D-SI system suggests that these measurements have the potential to assist in pre-operative planning and also as a measure of aesthetic outcome..
Di Micco, R., O'Connell, R.L., Barry, P.A., Roche, N., MacNeill, F.A. & Rusby, J.E.
(2017). Bilateral mammoplasty for cancer: Surgical, oncological and patient-reported outcomes. Eur j surg oncol,
INTRODUCTION: Bilateral mammoplasty (BM) can optimise oncological safety and aesthetic outcomes in women with large or ptotic breasts whose tumour to breast volume ratio or tumour location pose a challenge to standard breast-conserving therapy (BCT) and for whom mastectomy (with or without reconstruction) may be the only alternative. METHODS: We undertook a comprehensive analysis of surgical outcomes (complications according to the Clavien Dindo classification), acute radiation morbidity (Radiation Therapy Oncology Group classification), oncological outcomes, and patient satisfaction (BREAST-Q questionnaire) in women who underwent BM for breast cancer (BC) from June 2009-November 2014. RESULTS: 168 women were included. Median age was 55 years (range:33-84) and median tumour size at imaging 35 mm (range:0-170). Median specimen weight was 242 g (range 39-1824). The wise pattern technique was used in 87.5% of procedures. At least one complication occurred in 68 (40.5%) women, mostly Clavien Dindo grade 1. Grade 3 complications were infrequent (8.9%) but occurred mainly on the therapeutic mammoplasty (TM) side (p < 0.05). Complications were associated with higher BMI, specimen weight and longer time to radiotherapy (p < 0.05). Median follow-up was 37 months (range: 13-77). Local recurrence occurred in 3 (1.8%), distant metastases in 5 (3.0%), and 10 (6.0%) women have died. The median score for 'satisfaction with breasts' was 77 (range: 0-100). CONCLUSIONS: This study provides concurrent data on surgical, oncological and patient-reported outcomes. It offers evidence that BM is an effective treatment for breast cancer in large- or ptotic-breasted women..
Di Micco, R., O'Connell, R.L., Barry, P.A., Roche, N., MacNeill, F.A. & Rusby, J.E.
(2017). Standard wide local excision or bilateral reduction mammoplasty in large-breasted women with small tumours: Surgical and patient-reported outcomes. Eur j surg oncol,
INTRODUCTION: Oncoplastic breast surgery is used to extend the role of breast-conserving surgery (BCS) to women with an unfavourable tumour to breast volume ratio. However, large-breasted women with a relatively small breast cancer may be offered bilateral reduction mammoplasty (BRM) despite being suitable for standard BCS as the more complex surgery may have advantages in terms of patient satisfaction and reduced adverse effects of radiotherapy. PATIENT AND METHODS: This retrospective study evaluated surgical and patient-reported outcome measures (PROMs) in large-breasted women with early (<3 cm) breast cancer, who have undergone unilateral standard BCS or BRM. RESULTS: This series included 157 women, 87 in the unilateral BCS group and 70 in the BRM group. Median age was 60.2 years (range: 33-83.9). Median follow-up was 36 months (range: 9.8-76). Tumour size, rates of axillary dissection, adjuvant chemotherapy and tumour bed irradiation boost were significantly greater in the BRM group (p < 0.05). The surgical complication rate was not significantly different (43.7% vs. 34.3%, p = 0.253). Re-excision rates were higher in the standard BCS group (p < 0.05). Time to chemotherapy was similar, but time to radiotherapy was longer after BRM surgery (p = 0.025). Despite worse prognostic factors, more complex surgery and more aggressive adjuvant treatment, patients report better satisfaction and physical functioning and fewer adverse effects of radiotherapy after BRM than standard unilateral BCS. This difference was not statistically different in this small study (p > 0.05). CONCLUSION: Limitations of this study mean it can only be regarded as hypothesis-generating. Nonetheless, the trends merit a prospective study to investigate the optimal management of smaller breast cancers in larger-breasted women..
O'Connell, R.L., Di Micco, R., Khabra, K., Wolf, L., deSouza, N., Roche, N., Barry, P.A., Kirby, A.M. & Rusby, J.E.
(2017). The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT). Breast cancer research and treatment,
O'Connell, R.L., Di Micco, R., Khabra, K., Wolf, L., deSouza, N., Roche, N., Barry, P.A., Kirby, A.M. & Rusby, J.E.
(2017). The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT). Breast cancer res treat,
PURPOSE: To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT). METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction. RESULTS: 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and -0.229, respectively). CONCLUSION: Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes..
Peppe, A., Wilson, R., Pope, R., Downey, K. & Rusby, J.
(2017). The use of ultrasound in the clinical re-staging of the axilla after neoadjuvant chemotherapy (NACT). Breast,
INTRODUCTION: Ultrasound (US) is the imaging modality of choice for staging the axilla prior to surgery in patients with breast cancer (BC). High pathological complete response rates in the axilla after NACT mean a more conservative approach to surgery can be considered. Radiological re-staging is important in this decision making. After the presentation of results from ACOSOG Z1071 in December 2012, formal ultrasound re-assessment of the axilla after primary therapy was specifically requested in our institution. We report on the accuracy of axillary US (aUS) for identifying residual axillary disease post-NACT. METHODS: Data were collected on patients who had proven axillary disease prior to NACT and underwent axillary lymph node dissection after NACT between January 2013 and December 2015. Post-chemotherapy aUS reports and axillary pathology reports were classified as positive or negative for abnormal lymph nodes and for residual disease (cCR and pCR respectively). RESULTS: The sensitivity and specificity of aUS was 71% and 88% respectively. The negative predictive value (NPV) was 83%. The false negative rate was 29%. CONCLUSIONS: Axillary ultrasound provides clinically useful information post-NACT, which will guide surgical decision-making. Patients with aUS-negative axillae are likely to have a lower false negative rate of SLNB after NACT (Boughey et al.). However, aUS does not replace the need to identify and biopsy the nodes which were proven to be positive prior to NACT..
O'Connell, R.L., Rusby, J.E., Stamp, G.F., Conway, A., Roche, N., Barry, P., Khabra, K., Bonomi, R., Rapisarda, I.F. & Della Rovere, G.Q., et al.
(2016). Long term results of treatment of breast cancer without axillary surgery - Predicting a SOUND approach?. Eur j surg oncol,
BACKGROUND: Traditionally axillary surgery has been used to provide staging information and until recently was thought to improve loco-regional control. However, a more minimal approach to the axilla is now being adopted. The aim of this study was to assess long term outcomes of patients with 'low-risk' breast cancers who did not undergo any axillary surgery. 'Low-risk' criteria were: postmenopausal, <20 mm grade 1 or <15 mm grade 2, LVI-ve, ER +ve. METHODS: Women with invasive breast cancer that did not undergo any axillary surgery were identified. Patients were censored when an event or death occurred or at last follow-up at breast clinic or with their General Practitioner. RESULTS: Between 05/01/1995-20/11/2006, 194 patients (199 tumours) were operated upon without axillary surgery. Median follow-up was 10.4 years. 128 patients met low-risk criteria and 71 did not (patient choice = 42, medical fitness = 29). In the 'low risk' cohort there were two axillary recurrences, with a cumulative incidence of 0.8% and 1.9% at 5 and 10 years respectively. DDFS was 99.2% (94.1-99.9%), and 97% (90.0-99%) at 5 and 10 years respectively and DFS was 96.6% (91.1-98.7%) and 91.2% (82.6-95.6%). OS was 90.3% (95% CI: 83.6-94.4) and 75.5% (95% CI: 65.9-82.8) at 5 and 10 years respectively. CONCLUSION: Axillary recurrence and DDFS in this low-risk cohort is favourable. In the modern era of breast cancer management it is possible to define a group of women in whom axillary surgery can be omitted..
O'Connell, R.L., DiMicco, R., Khabra, K., O'Flynn, E.A., deSouza, N., Roche, N., Barry, P.A., Kirby, A.M. & Rusby, J.E.
(2016). Initial experience of the BREAST-Q breast-conserving therapy module. Breast cancer res treat,
PURPOSE: The most recently developed module of the BREAST-Q, a validated patient outcome measure, is for patients who have undergone breast-conserving therapy (BCT) for cancer. This aim of this study was to assess patient satisfaction and quality of life after BCT using BREAST-Q, investigate clinical risk factors for lower satisfaction and explore the relationship between patient satisfaction with the appearance of their breasts and the other domains of the BREAST-Q. METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate at the time of their annual surveillance mammogram. Clinicopathological data were collected from an electronic database. Linear regression was used to evaluate risk factors for lower satisfaction. Spearman's rho correlation coefficients were calculated to evaluate the relationship between domains. RESULTS: 200 women completed the questionnaire. Mean age was 60 years (SD 11.1). Time from surgery was 35.5 months (SD 17.8). Median score for 'Satisfaction with breasts' was 68 (interquartile range 55-80). Lowest scores were for 'sexual wellbeing' (57, IQR 45-66). On multivariate analysis, BMI at the time of surgery (p = 0.002), delayed wound healing (p = 0.001) and axillary surgery (p = 0.003) were independent risk factors for lower satisfaction. There was significant correlation between 'Satisfaction with breasts' and all other BREAST-Q domains. CONCLUSION: High BMI, delayed wound healing and axillary surgery are risk factors for lower patient satisfaction. This first publication reporting the whole dataset for the BREAST-Q BCT will serve as a benchmark for future studies of patient satisfaction following BCT..
Agha, R.A., Wellstead, G., Sagoo, H., Al Omran, Y., Barai, I., Rajmohan, S., Fowler, A.J., Orgill, D.P. & Rusby, J.E.
(2016). Nipple sparing versus skin sparing mastectomy: a systematic review protocol. Bmj open,
INTRODUCTION: Breast cancer has a lifetime incidence of one in eight women. Over the past three decades there has been a move towards breast conservation and a focus on aesthetic outcomes while maintaining oncological safety. For some patients, mastectomy is the preferred option. There is growing interest in the potential use of nipple sparing mastectomy (NSM). However, oncological safety remains unproven, and the benefits and indications have not been clearly identified. The objective of this systematic review will be to determine the safety and efficacy of NSM as compared with skin sparing mastectomy (SSM). METHODS AND ANALYSIS: All original comparative studies including; randomised controlled trials, cohort studies and case-control studies involving women undergoing either NSM or SSM for breast cancer will be included. Outcomes are primary-relating to oncological outcomes and secondary-relating to clinical, aesthetic, patient reported and quality of life outcomes. A comprehensive electronic literature search, designed by a search specialist, will be undertaken. Grey literature searches will also be conducted. Eligibility assessment will occur in two stages; title and abstract screening and then full text assessment. Each step will be conducted by two trained teams acting independently. Data will then be extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry. Data analysis will be undertaken to explore the relationship between NSM or SSM and preselected outcomes, heterogeneity will be assessed using the Cochrane tests. ETHICS AND DISSEMINATION: This systematic review requires no ethical approval. It will be published in a peer-reviewed journal. It will also be presented at national and international conferences. Updates of the review will be conducted to inform and guide healthcare practice and policy..
Muscara, F., Barry, P.A., Richardson, C. & Rusby, J.E.
(2015). Does lobular histology matter in the post-Z0011 era?. Breast,
O'Connell, R.L., Mohammed, K., Gui, G.P. & Rusby, J.E.
(2015). A case-control study of treatment choices made by doctors diagnosed with early breast cancer. Int j surg,
INTRODUCTION: Doctors who are diagnosed with breast cancer form a small subset of women with unique insight into their disease. The aim of this study was to compare key treatment decisions in medically-qualified doctors with equivalent degree-educated, matched controls diagnosed with early breast cancer. METHODS: Patients diagnosed with breast cancer between 01/01/2006 and 31/12/2011 were included and screened for occupation by 2 independent investigators. Allied health professionals with a medical background (e.g. nurses, physiotherapists) were excluded. Patient controls were matched by age, nodal status and grade. If there were more than 5 possible matches then those patients with the closest tumour size were selected. RESULTS: 5259 of 8623 patients had signed the generic research consent form. 619 of these were either doctors, or had received tertiary level education and could form appropriate controls. After exclusions, 46 medically-qualified doctors and 230 matched control patients were included in the analysis. No statistical differences in age or tumour characteristics were identified between doctors with breast cancer and matched controls. No differences were identified between the two groups in the uptake of mastectomy, chemotherapy, immediate breast reconstruction or post-mastectomy radiotherapy. CONCLUSION: Medically-qualified patients diagnosed with early breast cancer are no more likely to opt for mastectomy, chemotherapy, immediate breast reconstruction or post-mastectomy radiotherapy than non-medically-qualified controls. The level of information generally provided to patients with breast cancer is adequate for a similar decision to be made by control patients with equivalent levels of education, independent of any knowledge of pathology or understanding of the medical system that medically-qualified patients may possess..
O'Connell, R.L., Stevens, R.J., Harris, P.A. & Rusby, J.E.
(2015). Review of three-dimensional (3D) surface imaging for oncoplastic, reconstructive and aesthetic breast surgery. Breast,
Three-dimensional surface imaging (3D-SI) is being marketed as a tool in aesthetic breast surgery. It has recently also been studied in the objective evaluation of cosmetic outcome of oncological procedures. The aim of this review is to summarise the use of 3D-SI in oncoplastic, reconstructive and aesthetic breast surgery. An extensive literature review was undertaken to identify published studies. Two reviewers independently screened all abstracts and selected relevant articles using specific inclusion criteria. Seventy two articles relating to 3D-SI for breast surgery were identified. These covered endpoints such as image acquisition, calculations and data obtainable, comparison of 3D and 2D imaging and clinical research applications of 3D-SI. The literature provides a favourable view of 3D-SI. However, evidence of its superiority over current methods of clinical decision making, surgical planning, communication and evaluation of outcome is required before it can be accepted into mainstream practice. .
Muscara, F., Parvaiz, M.A. & Rusby, J.E.
(2015). A simple technique of breast tissue expander saline aspiration. Annals of the royal college of surgeons of england,
Muscara, F., Parvaiz, M.A. & Rusby, J.E.
(2015). A simple technique of breast tissue expander saline aspiration. Ann r coll surg engl,
Stevens, R.J., Stevens, S.G. & Rusby, J.E.
(2015). The "postcode lottery" for the surgical correction of gynaecomastia in NHS England. Int j surg,
INTRODUCTION: Action On Plastic Surgery (AOPS) criteria for funding of gynaecomastia surgery are: the patient should be post-pubertal, have a BMI ≤ 25 kg/m(2), endocrine and drug causes and breast cancer should be excluded and the patient should demonstrate psychological distress. We evaluated how NHS funding for gynaecomastia surgery varies between Clinical Commissioning Groups (CCGs) in England and whether there is a "postcode lottery". METHODS: The gynaecomastia surgery policies for 211 CCGs in NHS England were reviewed against the AOPS criteria and grouped according to their funding policies: group 1 (if criteria met, funding approved); group 2, (if criteria met, prior approval required); group 3 (no criteria, individual funding request only) and group 4 (no funding). RESULTS: Policies were available for all CCGs. Fifty-nine (28.0%) CCGs were in group 1, 87 (41.2%) in group 2, 44 (20.9%) in group 3 and 21 (10.0%) in group 4. Of those in groups 1 and 2, five (3.4%) CCGs used all six AOPS criteria. Approximately 70% CCGs with criteria (in groups 1 and 2) stipulated that the patient should be post-pubertal, have a BMI ≤ 25 kg/m(2) and endocrine and drug causes should be excluded. Breast cancer should be excluded in 51.4% and the patient should show psychological distress in 13.7% CCGs. Of those in groups 1 and 2, 118 (80.8%) CCGs specified additional criteria. CONCLUSIONS: CCGs do not use the AOPS criteria uniformly and restrict surgery according to their own criteria. Overall, there is a "postcode lottery" for gynaecomastia surgery within NHS England..
O'Connell, R.L. & Rusby, J.E.
(2015). Anatomy relevant to conservative mastectomy. Gland surg,
Knowledge of the anatomy of the nipple and breast skin is fundamental to any surgeon practicing conservative mastectomies. In this paper, the relevant clinical anatomy will be described, mainly focusing on the anatomy of the "oncoplastic plane", the ducts and the vasculature. We will also cover more briefly the nerve supply and the arrangement of smooth muscle of the nipple. Finally the lymphatic drainage of the nipple and areola will be described. An appreciation of the relevant anatomy, together with meticulous surgical technique may minimise local recurrence and ischaemic complications. .
O'Connell, R., Stevens, R., Khabra, K. & Rusby, J.
(2015). P104 3D surface imaging of the breasts Which patient position is most reproducible? (vol 41, pg S17, 2015). Ejso,
Muscara, F., Parvaiz, M.A. & Rusby, J.E.
(2015). A simple technique of breast tissue expander saline aspiration. Ann r coll surg engl,
Robertson, S.A., Rusby, J.E. & Cutress, R.I.
(2014). Determinants of optimal mastectomy skin flap thickness. Br j surg,
BACKGROUND: There is a limited evidence base to guide surgeons on the ideal thickness of skin flaps during mastectomy. Here the literature relevant to optimizing mastectomy skin flap thickness is reviewed, including anatomical studies, oncological considerations, factors affecting viability, and the impact of surgical technique and adjuvant therapies. METHODS: A MEDLINE search was performed using the search terms 'mastectomy' and 'skin flap' or 'flap thickness'. Titles and abstracts from peer-reviewed publications were screened for relevance. RESULTS: A subcutaneous layer of variable thickness that contains minimal breast epithelium lies between the dermis and breast tissue. The thickness of this layer may vary within and between breasts, and does not appear to be associated with obesity or age. The existence of a distinct layer of superficial fascia in the breast remains controversial and may be present in only up to 56 per cent of patients. When present, it may not be visible macroscopically, and can contain islands of breast tissue. As skin flap necrosis occurs in approximately 5 per cent of patients, a balance must be sought between removing all breast tissue at mastectomy and leaving reliably viable skin flaps. CONCLUSION: The variable and unpredictable thickness of the breast subcutaneous layer means that a single specific universal thickness for mastectomy skin flaps cannot be recommended. It may be that the plane between the subdermal fat and breast parenchyma is a reasonable guide for mastectomy flap thickness, but this may not always correspond to a subcutaneous fascial layer..
Mitchell, S., Klimberg, V.S., Ochoa, D., Rusby, J., Chang, D., Patel, R., Park, J., Korn, J.M. & Djohan, R.
(2014). Advanced locoregional therapies in breast. Ann surg oncol,
BACKGROUND: Advanced locoregional therapies continue to advance the treatment of breast cancer. These techniques are geared towards optimizing oncologic and aesthetic outcome as well as decreasing and treating morbidity. We present a selection of specialized locoregional therapies dedicated to the optimization of breast cancer treatment. METHODS: Locoregional therapies for breast cancer are presented to address breast conservation techniques, lipofilling techniques, reconstruction techniques for nipple-sparing mastectomy, re-irradiating the breast, axillary reverse mapping, and vascularized lymph node transfer. RESULTS: We present a synopsis of identified breast locoregional therapies targeted to address optimal oncologic and aesthetic outcome as well as decrease and treat morbidity..
O'Connell, R.L. & Rusby, J.E.
(2013). Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients: research highlight. Gland surg,
The rate of surgical site infection (SSI) after breast surgery is higher than expected for a 'clean procedure'. There is currently no consensus on the use of antibiotics, and as a result there is variation in use. An infection may compromise cosmesis and delay the start of adjuvant therapy. This research highlight reviews a recent paper by Gulluoglu and colleagues investigating the use of antibiotics in overweight and obese patients undergoing breast cancer surgery and also reviews the current literature on this important topic. .
O'Connell, R.L., Gui, G. & Rusby, J.E.
(2013). Doctors with breast cancer are more likely to opt for mastectomy: Fact or fiction?. Cancer research,
Kothari, M.S., Rusby, J.E., Agusti, A.A. & MacNeill, F.A.
(2012). Sentinel lymph node biopsy after previous axillary surgery: A review. Eur j surg oncol,
BACKGROUND: The utility of axillary lymph node dissection (ALND) in the management of breast cancer is currently under close scrutiny. At primary diagnosis the use of sentinel lymph node biopsy (SLNB) has restricted ALND for proven nodal disease, however the management of the axilla at local (in-breast) relapse is less clearly defined with many undergoing routine ALND. This review examines the role of SLNB in the re-operative setting with the objective of developing an axillary management algorithm for use at in-breast local relapse, and restricting ALND to node-positive recurrent cancers. METHODS: We reviewed published reports of SLNB at local relapse in women who had previously undergone axillary surgery either as lymph node biopsy, SLNB, axillary sampling (AS) or axillary lymph node dissection (ALND). RESULTS: There have been no randomised trials. Six reports with 327 cases were identified; of which 61% (199/327) had previous SLNB or ALND with <9 nodes removed. There was an overall successful sentinel lymph node (SLN) localisation at re-operation of 69% (227/327), range of 51-100%. In patients who have previously had limited axillary surgery (<9 nodes removed), the rate of successful SLN localisation was 83% (165/199), range of 68-100% and 142/165 (86%, range 80-100%) were node negative. In these highly selected patients no axillary recurrences were noted in those who had a negative SLN at re-operation after 26-46 months follow up. CONCLUSION: SLNB at in-breast relapse is feasible and safe with successful localisation related to the extent of previous axillary surgery..
Rusby, J., Agabiti, E., Waheed, S., Barry, P., Roche, N., Allum, W., Gui, G., MacNeill, F., Christaki, G., Osin, P., et al.
(2012). Comparison of sentinel lymph node positivity rates pre and post introduction of OSNA molecular analysis. Cancer research,
Rusby, J.E., Agabiti, E., Waheed, S., Barry, P., Roche, N., Allum, W., Gui, G., MacNeill, F., Christaki, G., Osin, P., et al.
(2012). Is OSNA mRNA copy number in sentinel lymph node biopsy predictive of further disease in the axilla?. Cancer research,
Chakravorty, A., Sanmugalingam, N., Shrestha, A., Thomee, E., Rusby, J., Roche, N. & MacNeill, F.
(2011). Axillary nodal yields: a comparison between primary clearance and completion clearance after sentinel lymph node biopsy in the management of breast cancer. Eur j surg oncol,
AIMS: Axillary nodal status is the most important prognostic indicator which in turn influences adjuvant therapy and long term outcomes. The aim of this study was to compare total nodal yields from primary axillary lymph node dissection (pALND) with completion ALND after a cancer positive SLNB: either concurrently (cALND) following intra-operative assessment (IOA) of the SLN's or as a delayed procedure (dALND) when the SLN was found to be cancer positive on post-operative histological examination. METHODS: All axillary procedures performed between May 2006 and September 2009 were identified from a prospective database and categorised into four groups: SLNB with no further axillary surgery, pALND, cALND and dALND. Total nodal yield was the sum of SLN/s and ALND yields. RESULTS: Of 1025 axillary procedures, ALND accounted for 332 (32.4%) of which 207 (62.3%) underwent pALND, 43 (12.9%) cALND, and 82 (24.6%) dALND. Median nodal yields were 15.0, 16.0 and 14.5 respectively (p = 0.3). CONCLUSION: Total nodal yields for primary, concurrent and delayed ALND were comparable suggesting completion dALND performed as a second operation does not compromise axillary staging..
Rusby, J.E., Gough, J., Harris, P.A. & MacNeill, F.A.
(2011). Oncoplastic multidisciplinary meetings: a necessity or luxury?. Ann r coll surg engl,
Although there is scant evidence to support multidisciplinary meetings in any cancer specialty, they are now regarded as best practice. We believe the oncoplastic multidisciplinary meeting plays a similarly important role, consolidating oncoplastic multidisciplinary working and allowing transparent decision making, standardisation of care and recording of results. This may drive oncoplastic surgery to an evidence-based position from which oncoplastic excellence can be achieved..
Rusby, J.E., Smith, B.L. & Gui, G.P.
(2010). Nipple-sparing mastectomy. Br j surg,
BACKGROUND: Although effective local control is the primary goal of surgery for breast cancer, the long-term aesthetic outcome is also important. Nipple-sparing mastectomy aims to address this, but there is no consensus on its clinical application. Evidence relating to oncological safety, surgical technique and early data on aesthetic outcome was reviewed. METHODS: The review was based on a PubMed search using the terms 'nipple-sparing' or 'subcutaneous mastectomy' and 'breast cancer'. RESULTS: Large pathological studies report occult nipple involvement with cancer in 5.6-31 per cent, reflecting variation in inclusion criteria. Recent clinical series with careful patient selection report local recurrence in less than 5 per cent of patients. The incidence of cancer in the retained nipple after risk-reducing mastectomy is less than 1 per cent. Nipple necrosis rates range up to 8 and 16 per cent for total and partial necrosis respectively. Variations in outcome result from differences in extent of resection, placement of incisions and type of breast reconstruction. CONCLUSION: Nipple-sparing mastectomy is an acceptable technique for women undergoing risk-reducing mastectomy. In the therapeutic setting, it may be offered to patients with smaller tumours far from the nipple and favourable pathological features. Women should be counselled about nipple necrosis and the potential for local recurrence..
Rusby, J.E., Waters, R.A., Nightingale, P.G. & England, D.W.
(2010). Immediate breast reconstruction after mastectomy: what are the long-term prospects?. Ann r coll surg engl,
INTRODUCTION: Immediate breast reconstruction after mastectomy has known psychological and financial advantages but it is difficult to compare the outcome of various methods of reconstruction. Re-operation rates are an objective measure of surgical intervention required to attain and maintain acceptable cosmesis. PATIENTS AND METHODS: A series of 95 patients (110 immediate reconstructions) was analysed for number of re-operations required within 5 years of initial surgery, magnitude of procedures, 'survival' of the reconstruction and effect of radiotherapy. RESULTS: Although more intervention was seen in patients with implant-based reconstruction and the time-course over which autologous and implant-based reconstructions fail is different these did not reach statistical significance. Radiotherapy has a significant effect on failure of implant-based reconstruction. CONCLUSIONS: Long-term, large studies of immediate reconstruction are required to assess adequately the impact of type of reconstruction on re-operation rates. The National Mastectomy and Breast Reconstruction Audit is ideally placed to provide answers to remaining questions about longevity of immediate breast reconstruction and the effect that late failure has on patient satisfaction..
Rusby, J.E. & Gui, G.P.
(2010). Nipple-sparing mastectomy in women with large or ptotic breasts. J plast reconstr aesthet surg,
Javid, S.H., Kirstein, L.J., Rafferty, E., Lipsitz, S., Moore, R., Rusby, J.E., Murphy, C.D., Hughes, K.S., Specht, M.C., Taghian, A.G., et al.
(2009). Outcome of multiple-wire localization for larger breast cancers: do multiple wires translate into additional imaging, biopsies, and recurrences?. Am j surg,
BACKGROUND: Breast conservation is possible in breast cancer patients whose mammographic lesions are large enough to require multiple localizing wires for excision. METHODS: A retrospective review of 112 patients who underwent multiple-wire and 160 controls who underwent single-wire lumpectomy for breast cancer. Rates of in-breast recurrence, metastasis, and additional imaging and biopsy procedures were calculated. RESULTS: The median follow-up was 24 months. One multiple-wire and 2 single-wire patients developed in-breast recurrences (P = .84). No distant metastases developed among the multiple-wire patients. Additional follow-up imaging was obtained in 29% of multiple-wire and 22% of single-wire cases (P = .1). Seven (6%) of the multiple-wire and 11 (6%) of the single-wire cases underwent biopsy (P = .94). CONCLUSIONS: We found no increased risk of early local recurrence, metastasis, or additional imaging or biopsies in patients requiring multiple-wire localization for lumpectomy. Breast conservation should be considered a safe option even for patients with mammographically extensive lesions..
Brachtel, E.F., Rusby, J.E., Michaelson, J.S., Chen, L.L., Muzikansky, A., Smith, B.L. & Koerner, F.C.
(2009). Occult nipple involvement in breast cancer: clinicopathologic findings in 316 consecutive mastectomy specimens. J clin oncol,
PURPOSE: Although breast-conserving surgery is a standard approach for patients with breast cancer, mastectomy often becomes necessary. Surgical options now include nipple-sparing mastectomy but its oncological safety is still controversial. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients with the retroareolar margin as possible indicator of nipple involvement. PATIENTS AND METHODS: Three hundred sixteen consecutive mastectomy specimens (232 therapeutic, 84 prophylactic) with grossly unremarkable nipples were evaluated by coronal sections through the entire nipple and subareolar tissue. Extent and location of nipple involvement by carcinoma was assessed with the tissue deep to the skin as potential retroareolar en-face resection margin. RESULTS: Seventy-one percent of nipples from therapeutic mastectomies showed no pathologic abnormality, 21% had ductal carcinoma in situ (DCIS), invasive carcinoma (IC), or lymphovascular invasion (LVI), and 8% lobular neoplasia (lobular carcinoma in situ). Human epidermal growth factor receptor 2 amplification, tumor size, and tumor-nipple distance were associated with nipple involvement by multivariate analysis (P = .0047, .0126, and .0176); histologic grade of both DCIS (P = .002) and IC (P = .03), LVI (P = .03), and lymph node involvement (P = .02) by univariate analysis. Nipple involvement by IC or DCIS was identified in the retroareolar margin with a sensitivity of 0.8 and a negative predictive value of 0.96. None of the 84 prophylactic mastectomies showed nipple involvement by IC or DCIS. CONCLUSION: Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy..
Rusby, J.E., Kirstein, L.J., Brachtel, E.F., Michaelson, J.S., Koerner, F.C. & Smith, B.L.
(2008). Nipple-sparing mastectomy: lessons from ex vivo procedures. Breast j,
Moderate size series have reported successful nipple-sparing mastectomy using a variety of surgical techniques. This study aimed to understand which aspects of these techniques are safe, necessary, and successful. Eight skin-sacrificing mastectomy specimens were used as ex vivo models of nipple-sparing mastectomy. After inking the resection margins of the specimen, the skin ellipse was elevated in the subcutaneous plane using a scalpel. The retroareolar breast tissue was taken as a margin specimen. The nipple was inverted and the nipple core removed. The hollowed-out nipple remnant (which would have remained with the patient in a true nipple-sparing mastectomy) was submitted for confirmatory histopathologic analysis. Precise identification of the duct margin directly beneath the nipple proved difficult once the duct bundle had been divided. Successful retroareolar margin identification was achieved by grasping the duct bundle with atraumatic forceps as soon as it became exposed. A cut made below and above the forceps resulted in a full cross-section of the duct bundle. Nipple core tissue was difficult to excise in one piece and cannot be oriented, thus complete evaluation of the specimen required examination of multiple levels. Histologic artifacts caused by freezing may be present in frozen sections of nipple core and retroareolar margin specimens; the impact of such changes must be considered when developing institutional protocols for this procedure. Evaluation of the hollowed-out nipple revealed that the inverted nipple must be substantially thinned to remove all ducts. Modification of technique resulted in more complete excision of duct tissue. This series of ex vivo procedures provides information that can be used to modify surgical and pathologic techniques for nipple-sparing mastectomy. When performing nipple-sparing mastectomy for breast cancer, these measures may be advisable as complements to careful patient selection..
Rusby, J.E., Brachtel, E.F., Othus, M., Michaelson, J.S., Koerner, F.C. & Smith, B.L.
(2008). Development and validation of a model predictive of occult nipple involvement in women undergoing mastectomy. Br j surg,
BACKGROUND: This prospective study aimed to build a predictive model using preoperative information to aid selection for nipple-sparing mastectomy. METHODS: Two hundred consecutive skin-sparing mastectomy specimens without overt nipple involvement were evaluated. Demographic, preoperative pathology and imaging information was collected. Nipple specimens (2 x 2 x 2 cm) were sectioned at 3-mm intervals. Haematoxylin and eosin-stained slides were examined by a breast pathologist for involvement by tumour. Logistic regression analyses of 65 therapeutic procedures identified factors associated with occult involvement and created a predictive model. This was tested on specimens from a further 65 therapeutic procedures. RESULTS: Occult nipple involvement was noted in 32 (24.6 per cent) of 130 mastectomy specimens. In the training set, imaging diameter of the lesion and its distance from the nipple predicted nipple involvement on univariable analysis (P = 0.011 and P = 0.014 respectively). The multivariable logistic regression model was validated in the test set. The areas under the receiver-operating characteristic curve were 0.824 and 0.709 for the training and test sets respectively. CONCLUSION: Three-quarters of women undergoing mastectomy did not have occult nipple involvement. A clinical tool including tumour size and distance from the nipple has been developed to improve patient selection for nipple-sparing mastectomy..
Kopans, D.B. & Rusby, J.E.
(2008). Cutaneous caves and subcutaneous adipose columns in the breast: radiologic-pathologic correlation. Radiology,
PURPOSE: To investigate the histologic correlations of the innumerable 2-3-mm radiolucencies that project over the breast, as seen on mammograms. MATERIALS AND METHODS: With institutional review board approval and HIPAA compliance, this work involved detailed x-ray imaging of discarded tissue from two mastectomy specimens, together with histologic examination of the skin and subcutaneous fat and evaluation of the skin during reduction mammoplasty surgery in two patients. RESULTS: Comparison of the histologic findings with the findings on x-ray images demonstrated that the lucencies seen by using mammography are cutaneous caves in the underside of the dermis into which insert columns of fat projecting up from the subcutaneous adipose tissue. This finding was confirmed with evaluation of the skin during reduction surgery. CONCLUSION: As far as is known, this is the first description of a complex of anatomic structures that explain radiolucencies evident by using mammography..
Rusby, J.E. & Smith, B.L.
(2008). Unanswered questions in nipple-sparing mastectomy. Surg oncol,
Golshan, M., Rusby, J., Dominguez, F. & Smith, B.L.
(2007). Breast conservation for male breast carcinoma. Breast,
Male breast cancer in general is treated by modified radical mastectomy. Data have emerged supporting the replacement of the axillary lymph node dissection by a sentinel lymph node biopsy in the male patient with breast carcinoma. Local therapy in the breast continues to be primarily mastectomy. The reasons suggested for this include the central location of many of the male breast tumors and the paucity of breast tissue. Our experience with breast conservation over the last decade in male breast carcinoma and a review of the literature is outlined here. Between 1996 and 2006, seven men underwent breast conservation for breast carcinoma and to date with a median follow-up of 67 months, there have been no local recurrences. Breast carcinoma in males can be treated with breast conservation with acceptable local recurrence. Breast-conserving surgery in male breast cancer patients should be considered an option in patients without overt nipple/areolar involvement..
Rusby, J.E., Brachtel, E.F., Michaelson, J.S., Koerner, F.C. & Smith, B.L.
(2007). Breast duct anatomy in the human nipple: three-dimensional patterns and clinical implications. Breast cancer res treat,
BACKGROUND: The anatomy of the nipple has become clinically relevant. Diagnostic techniques access the breast through nipple ducts and surgeons offer nipple-sparing mastectomy. There is variation in the number of ducts reported and little is known about the spatial location of ducts, their size, and their relationship to orifices on the surface. METHODS: Nipple specimens were taken from 129 consecutive mastectomies. Each was sectioned coronally into 3 mm blocks and one section was prepared from each block. The number of ducts and cross-sectional areas of nipple and duct 'bundle' were recorded. Three nipples were sectioned at 50 mum intervals and digitally reconstructed in three dimensions. RESULTS: The median number of ducts was 23 (interquartile range 19-28). Reconstructions and summary data from 25 nipples show a central duct bundle narrowing to form a 'waist' as the ducts enter breast parenchyma. A three-dimensional reconstruction focusing on one nipple tip demonstrated 29 ducts arising from 15 orifices. Beneath the skin, most ducts are very narrow, gradually becoming larger deeper within the nipple. CONCLUSIONS: This work demonstrates that many ducts share a few common openings onto the surface of the nipple, explaining the observed discrepancy between number of ducts and of orifices. Neither duct diameter nor position predicts whether a duct system will terminate close to the nipple or pass deeper into the breast. These new insights into nipple anatomy will be of use in considering the reliability of a ductal approach to diagnosis and in planning nipple-sparing mastectomy..
Rusby, J.E., Smith, B.L., Dominguez, F.J. & Golshan, M.
(2006). Sentinel lymph node biopsy in men with breast cancer: a report of 31 consecutive procedures and review of the literature. Clin breast cancer,
PURPOSE: We present our experience with sentinel lymph node (SLN) biopsy in men with breast cancer and review the literature published to date. Consecutive men with breast cancer undergoing SLN biopsy were identified in our prospectively maintained database. A PubMed search for "male breast cancer" and "sentinel node biopsy" was performed. PATIENTS AND METHODS: Thirty patients underwent 31 SLN biopsy procedures between 1996 and 2006. Twenty-five patients presented with a palpable mass, and 13 underwent surgical biopsy for diagnosis. The sentinel lymph node was successfully identified in 90%; 61% of SLN biopsies were positive and, in 65% of this group, the sentinel node was the only positive node. RESULTS: Combined data from the literature from 110 procedures resulted in an identification rate of 96%, positive sentinel nodes in 45% and the sentinel node as the only positive node in 56%. Only 13 patients underwent completion axillary node dissection after a negative SLN biopsy; none were false negatives. This series extends previous knowledge about SLN biopsy in men with respect to diagnostic biopsy, type of mapping agent, lymphoscintigraphy, and location of injection site. The identification rate mirrors that of large randomized trials of women with breast cancer. CONCLUSION: The high rate of lymph node-positive disease, even in this series of patients with clinically node-negative disease, reflects the later presentation of breast cancer in men..
Sutak, J., Armstrong, J.S. & Rusby, J.E.
(2005). Squamous cell carcinoma arising in a tall cell papillary carcinoma of the thyroid. J clin pathol,
Transformation of differentiated thyroid cancer into poorly differentiated carcinoma is rare. This report describes a case in which preoperative fine needle aspiration suggested a squamous cell carcinoma whereas needle core biopsy favoured an undifferentiated carcinoma of probable thyroid origin. Histology of the subsequent total thyroidectomy specimen revealed a biphasic tumour comprising areas of tall cell papillary carcinoma merging with moderately to poorly differentiated squamous cell carcinoma. The immunohistochemical findings are discussed in detail..
Rusby, J.E., Welch, C.M. & Lamparelli, M.J.
(2005). Fast-track surgery (Br J Surg 2005; 92: 3-4). Br j surg,
Stevens, R.J., Rusby, J.E. & Graham, M.D.
(2003). Periorbital cellulitis with breast cancer. J r soc med,
Wong, L.S., Rusby, J. & Ismail, T.
(2001). Left-sided gall bladder: a diagnostic and surgical challenge. Anz j surg,
Wong, L.S., Rusby, J., Bassi, U.A., Rowlands, D. & Ismail, T.
(2000). Stromal tumour of the small bowel. J r soc med,
Klein, N., Sen, A., Rusby, J., Ratip, S., Modell, B. & Olivieri, N.F.
(1998). The psychosocial burden of Cooley's anemia in affected children and their parents. Ann n y acad sci,
Byrnes, A.P., Rusby, J.E., Wood, M.J. & Charlton, H.M.
(1995). Adenovirus gene transfer causes inflammation in the brain. Neuroscience,
We report that injecting an E1-deleted, non-replicating, human adenovirus type 5 vector into the brain leads to an inflammatory response. Much of this inflammation is induced directly by the virion particles themselves rather than through the expression of new proteins from the vector. The severity of inflammation was found to depend on the strain of inbred rat used: PVG rats have less inflammation than AO rats in response to a vector injection. Twelve hours after injection of adenovirus vectors into the striatum of AO rats, leukocytes were seen marginating to the walls of nearby blood vessels. By two days there was a large increase in major histocompatibility complex class I expression and a heavy infiltration of leukocytes, mainly macrophages and T cells. Retrograde transport of adenovirus to neurons of the substantia nigra was associated with a delayed and less intense inflammation at this distant site. Although AO and PVG rats showed comparable responses in the striatum up to six days, at later times PVG rats had less intense inflammation. In spite of the inflammatory response, vector-driven expression of the marker protein beta-galactosidase and an adenovirus early protein was seen for at least two months following the injection, although expression declined with time. The observation that adenovirus gene transfer leads to an inflammatory response in the brain must be taken into account when planning and interpreting experiments with these vectors. Furthermore, we conclude that using an appropriate strain of rat can diminish some aspects of the inflammation..