Publications
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St John ER, Al-Khudairi R, Ashrafian H, et al., 2016, Diagnostic accuracy of intraoperative techniques for margin assessment in breast cancer surgery: a meta-analysis, Annals of Surgery, Vol: 265, Pages: 300-310, ISSN: 1528-1140
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.
Modi HN, Singh H, Yang GZ, et al., 2016, “Coping or choking”: sustained prefrontal activation and improved laparoscopic performance under time pressure, 9th Hamlyn Symposium on Medical Robotics
Modi HN, Singh H, Orihuela-Espina F, et al., 2016, Cortical haemodynamic changes associated with high and low cognitive demand in surgeons, 22nd Annual Meeting of the Organisation for Human Brain Mapping, Publisher: Organization for Human Brain Mapping
Boshier PRB, Sayers R, Hadjiminas D, et al., 2016, 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, Experimental Hematology and Oncology, Vol: 5, ISSN: 2162-3619
BackgroundInflammatory 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 presentationThe 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.ConclusionThis 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 potent
Singh H, modi H, Yang GZ, et al., 2016, A surgeon’s brain switch: cortical dynamics of cognitive load in surgeons, Publisher: Graz University of Technology, Pages: 163-163
Andreu-Perez J, Leff DR, Shetty K, et al., 2016, Disparity in frontal lobe connectivity on a complex bimanual motor task aids in classification of operator skill level., Brain Connectivity, Vol: 6, Pages: 375-388, ISSN: 2158-0022
Objective metrics of technical performance (e.g., dexterity, time, and path length) are insufficient to fully characterize operator skill level, which may be encoded deep within neural function. Unlike reports that capture plasticity across days or weeks, this articles studies long-term plasticity in functional connectivity that occurs over years of professional task practice. Optical neuroimaging data are acquired from professional surgeons of varying experience on a complex bimanual coordination task with the aim of investigating learning-related disparity in frontal lobe functional connectivity that arises as a consequence of motor skill level. The results suggest that prefrontal and premotor seed connectivity is more critical during naïve versus expert performance. Given learning-related differences in connectivity, a least-squares support vector machine with a radial basis function kernel is employed to evaluate skill level using connectivity data. The results demonstrate discrimination of operator skill level with accuracy ≥0.82 and Multiclass Matthew's Correlation Coefficient ≥0.70. Furthermore, these indices are improved when local (i.e., within-region) rather than inter-regional (i.e., between-region) frontal connectivity is considered (p = 0.002). The results suggest that it is possible to classify operator skill level with good accuracy from functional connectivity data, upon which objective assessment and neurofeedback may be used to improve operator performance during technical skill training.
Shetty K, Leff DR, Orihuela-Espina F, et al., 2016, Persistent Prefrontal Engagement Despite Improvements in Laparoscopic Technical Skill, JAMA Surgery, Vol: 151, Pages: 682-684, ISSN: 2168-6262
Teaching and assessment of laparoscopic skills are currently essential components of surgical training. The Fundamentals of Laparoscopic Surgery (FLS) is a widely adopted training program based on expert-derived benchmarks; technical skills are assessed and completion is a mandatory criterion for general surgery board certification in the United States.1 However, is attainment of technical proficiency synonymous with being a safe surgeon? Intraoperative errors persist and are thought to be related to errors in cognition2 as opposed to technical failure per se. The prefrontal cortex (PFC) is a brain region associated with attention and executive function serving as a scaffold to support novel task demands during effortful unrefined performance.3 Studies examining cortical correlates of technical skills acquisition have observed predictable attenuation in PFC response alongside improvement in technical performance4,5; however, this has not been adequately tested for challenging laparoscopic skills.
Thiruchelvam P, Cleator S, Wood S, et al., 2016, Primary Radiotherapy and DIEP [Deep Inferior Epigastric Perforator] Flap Reconstruction (PRADA) Study: Findings From the Pilot Study, 17th Annual Meeting of the American-Society-of-Breast-Surgeons, Publisher: SPRINGER, Pages: 159-160, ISSN: 1068-9265
St John ER, Al-Khudairi R, Balog J, et al., 2016, Rapid evaporative ionisation mass spectrometry towards real time intraoperative oncological margin status determination in breast conserving surgery, 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium, Publisher: American Association for Cancer Research, Pages: P2-12-20-P2-12-20, ISSN: 1538-7445
St John ER, Al-Khudairi R, Balog J, et al., 2016, Abstract P2-12-20: rapid evaporative ionisation mass spectrometry towards real time intraoperative oncological margin status determination in breast conserving surgery, 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium, Publisher: American Association for Cancer Research, ISSN: 1538-7445
Modi HN, Leff DR, Singh H, et al., 2016, The influence of cognitive load on technical ability among surgical trainees, Association of Surgeons in Training International Conference
Leff DR, Shetty K, Yang GZ, et al., 2016, Persistent Attentional Demands Despite Laparoscopic Skills Acquisition, JAMA Surgery, ISSN: 2168-6262
Flindall IR, Leff DR, Pucks N, et al., 2016, The Preservation of Cued Recall in the Acute Mentally Fatigued State: A Randomised Crossover Study., World Journal of Surgery, Vol: 40, Pages: 56-65, ISSN: 1432-2323
PURPOSE: The objective of this study is to investigate the impact of acute mental fatigue on the recall of clinical information in the non-sleep-deprived state. Acute mental fatigue in the non-sleep-deprived subject is rarely studied in the medical workforce. Patient handover has been highlighted as an area of high risk especially in fatigued subjects. This study evaluates the deterioration in recall of clinical information over 2 h with cognitively demanding work in non-sleep-deprived subjects. METHOD: A randomised crossover study involving twenty medical students assessed free (presentation) and cued (MCQ) recall of clinical case histories at 0 and 2 h under low and high cognitive load using the N-Back task. Acute mental fatigue was assessed through the Visual Analogue Scale, Stanford Scale and NASA-TLX Mental Workload Rating Scale. RESULTS: Free recall is significantly impaired by increased cognitive load (p < 0.05) with subjects demonstrating perceived mental fatigue during the high cognitive load assessment. There was no significant difference in the amount of information retrieved by cued recall under high and low cognitive load conditions (p = 1). DISCUSSION: This study demonstrates the loss of clinical information over a short time period involving a mentally fatiguing, high cognitive load task. Free recall for the handover of clinical information is unreliable. Memory cues maintain recall of clinical information. This study provides evidence towards the requirement for standardisation of a structured patient handover. The use of memory cues (involving recognition memory and cued recall methodology) would be beneficial in a handover checklist to aid recall of clinical information and supports evidence for their adoption into clinical practice.
Leff DR, Petrou G, Mavroveli S, et al., 2015, Validation of an oncoplastic breast simulator for assessment of technical skills in wide local excision., British Journal of Surgery, Vol: 103, Pages: 207-217, ISSN: 1365-2168
BACKGROUND: Simulation enables safe practice and facilitates objective assessment of technical skills. However, simulation training in breast surgery is rare and assessment remains subjective. The primary aim was to evaluate the construct validity of technical skills assessments in wide local excision (WLE). METHODS: Surgeons of different grades performed a WLE of a 25-mm palpable tumour on an in-house synthetic breast simulator. Procedures were videotaped (blinded), reviewed retrospectively, and independently rated against a procedure-specific global rating scale by two consultant breast surgeons. Specimen radiographs were obtained and the macroscopic distance from the 'tumour' edge to the resection margin was recorded in four cardinal directions. Expert consensus was used to construct an Oncoplastic Deviation Score (ODS), assigning points for excessively wide (more than 10 mm) and, conversely, close (less than 5 mm) macroscopic margins. RESULTS: Thirty-four surgeons (12 consultant surgeons, 12 specialty trainees and 10 core trainees) participated in the study. Video-based rating scores varied hierarchically with operator expertise (P < 0·050). Inter-rater reliability was excellent (α ≥ 0·80, P < 0·050 for all scales), and inter-rater agreement was moderate (κ = 0·132-0·361, P < 0·050 for all scales). Statistically significant differences were observed on pairwise comparisons between each grade of surgeon in scores for 'exposure', 'skin flap development', 'glandular remodelling', 'skin closure' and 'final product review' (P < 0·050). Consultants received significantly fewer ODS points than specialty trainees (P = 0·012) and core trainees (P = 0·028). Compared with experts (median 9·0 mm), wider margins were observed amongst specialty trainees (median 12·0 mm) and narrower margins amongst core trainees (median 7·1 mm) (P = 0·001). CONCLUSION: Video r
Crewther BT, Shetty K, Jarchi D, et al., 2015, Skill acquisition and stress adaptations following laparoscopic surgery training and detraining in novice surgeons., Surgical Endoscopy, Vol: 30, Pages: 1961-2968, ISSN: 0930-2794
BACKGROUND: Surgical training and practice is stressful, but adaptive changes in the stress circuitry (e.g. perceptual, physiological, hormonal, neural) could support skill development. This work examined skill acquisition and stress adaptations in novice surgeons during laparoscopic surgery (LS) training and detraining. METHODS: Twelve medical students were assessed for skill performance after 2 h (BASE), 5 h (MID) and 8 h (POST) of LS training in weeks 1-3, and then after 4 weeks of no training (RETEST). The stress outcomes included state anxiety, perceived stress and workload, heart rate (HR), heart rate variability (HRV), and salivary testosterone and cortisol concentrations. Functional near-infrared spectroscopy was used to assess cortical oxygenation change, as a marker of prefrontal cortex (PFC) activity. RESULTS: Skill performance improved in every session from BASE (p < 0.01), with corresponding decreases in state anxiety, stress, workload, low- and high-frequency HRV in the MID, POST and/or RETEST sessions (p < 0.05). Left and right PFC were symmetrically activated within each testing session (p < 0.01). The stress and workload measures predicted skill performance and changes over time (p < 0.05), with state anxiety, mean HR and the HRV measures also showing some predictive potential (p < 0.10). CONCLUSIONS: A 3-week LS training programme promoted stress-related adaptations likely to directly, or indirectly, support the acquisition of new surgical skills, and many outcomes were retained after a 4-week period without further LS training. These results have implications for medical training and education (e.g. distributed training for skill development and maintenance, stress resource and management training) and highlighted possible areas for new research (e.g. longitudinal stress and skill profiling).
Leff DR, James D, Orihuela-Espina F, et al., 2015, The impact of expert visual guidance on trainee visual search strategy, visual attention and motor skills, Frontiers in Human Neuroscience, Vol: 9, ISSN: 1662-5161
Minimally invasive and robotic surgery changes the capacity for surgical mentors to guide their trainees with the control customary to open surgery. This neuroergonomic study aims to assess a “Collaborative Gaze Channel” (CGC); which detects trainer gaze-behaviour and displays the point of regard to the trainee. A randomised crossover study was conducted in which twenty subjects performed a simulated robotic surgical task necessitating collaboration either with verbal (control condition) or visual guidance with CGC (study condition). Trainee occipito-parietal (O-P) cortical function was assessed with optical topography (OT) and gaze-behaviour was evaluated using video-oculography. Performance during gaze-assistance was significantly superior [biopsy number: (mean ± SD): control=5·6±1·8 vs. CGC=6·6±2·0; p< 0.05] and was associated with significantly lower O-P cortical activity [∆HbO2 mMol x cm [median (IQR)] control = 2.5 (12.0) vs. CGC 0.63 (11.2), p < 0.001]. A random effect model confirmed the association between guidance mode and O-P excitation. Network cost and global efficiency and global efficiency were not significantly influenced by guidance mode. A gaze channel enhances performance, modulates visual search, and alleviates the burden in brain centres subserving visual attention and does not induce changes in the trainee's O-P functional network observable with the current OT technique. The results imply that through visual guidance, attentional resources may be liberated, potentially improving the capability trainees to attend to other safety critical events during the procedure.
Flindall IR, Leff DR, Goodship J, et al., 2015, Structured Cues or Modafinil for Fatigue Amelioration in Clinicians: A Double Blind Randomized Controlled Trial of Critical Clinical Information Recall in Fatigued Clinicians, 70th Annual Sessions of the Scientific Forum and Annual Clinical Congress of the American-College-of-Surgeons, Publisher: Elsevier, Pages: S56-S56, ISSN: 1072-7515
Despite attempts to minimize sleep deprivation through roster redesign, evidence suggests that fatigue remains prevalent. The wake-promoting agent modafinil improves cognition in the sleep-deprived fatigued state and may improve information recall in fatigued non-sleep–deprived clinicians.
Leff DR, Bottle A, Mayer E, et al., 2015, Trends in immediate postmastectomy breast reconstruction in the United Kingdom, Plastic and Reconstructive Surgery, Global Open, Vol: 3, ISSN: 2169-7574
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 (R2 = 0.97) than a linear function (R2 = 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.
Leff DR, Yang G-Z, 2015, Big Data for Precision Medicine, ENGINEERING, Vol: 1, Pages: 277-279, ISSN: 2095-8099
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- Citations: 24
Chang TP, Leff DR, Shousha S, et al., 2015, Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning, Breast Cancer Research and Treatment, Vol: 153, Pages: 299-310, ISSN: 1573-7217
Current techniques for assessing the adequacyof tumour excision during breast conserving surgery do notprovide real-time direct cytopathological assessment of theinternal cavity walls within the breast. This study investigatesthe ability of probe-based confocal laser endomicroscopy(pCLE), an emerging imaging tool, to image themorphology of neoplastic and non-neoplastic breast tissues,and determines the ability of histopathologists andsurgeons to differentiate these images. Freshly excisedtumour samples and adjacent non-diseased sections from50 consenting patients were stained with 0.01 % acriflavinehydrochloride and imaged using pCLE. All discerniblepCLE features were cross-examined with conventionalhistopathology. Following pattern recognition training, 17histopathologists and surgeons with no pCLE experienceinterpreted 50 pCLE images independently whilst blindedto histopathology results. Three-hundred and fifty pCLEimage mosaics were analysed. Consistent withhistopathology findings, the glandular structures, adipocytesand collagen fibres of normal breast were readilyvisible on pCLE images. These were distinguishable fromthe morphological architecture exhibited by invasive andnon-invasive carcinoma. The mean accuracy of pCLEimage interpretation for histopathologists and surgeons was94 and 92 %, respectively. Overall, inter-observer agreementfor histopathologists was ‘almost perfect’, j = 0.82;and ‘substantial’ for surgeons, j = 0.74. pCLE morphologicalfeatures of neoplastic and non-neoplastic breasttissues are readily visualized and distinguishable with highaccuracy by both histopathologists and surgeons. Furtherresearch is required to investigate a potential role for theuse of pCLE intraoperatively for in situ detection ofresidual cancerous foci, thereby guiding operating decision-makingbased on real-time breast cavity scanning.
Modi HN, Singh H, Leff DR, et al., 2015, “Blushing when the heat is on”: can cognitive load in the surgeon’s brain be captured?, 9th London Surgical Symposium
Leff DR, Ho C, Thomas H, et al., 2015, A multidisciplinary team approach minimises prophylactic mastectomy rates, European Journal of Surgical Oncology (EJSO), Vol: 41, Pages: 1005-1012, ISSN: 0748-7983
BackgroundProphylactic mastectomy (PM) has become increasingly common but is not without complications especially if accompanied by reconstructive surgery. In patients with sporadic unilateral breast cancer, contralateral PM offers no survival advantage. Multidisciplinary team (MDT) communication and interaction may facilitate shared decision-making and curtail PM rates. The aim of this study was investigate the effect of a regional MDT meeting on PM decision-making.MethodsWe conducted an observational study involving retrospective review of prospectively recorded MDT meeting records for a 151 patient requests for PM from 2011 to 2014. Final MDT decisions were recorded as PM ‘accepted’, ‘declined’ or ‘pending’. For MDT sanctioned requests, the factors justifying PM were recorded. Where PM was declined, justification for MDT refusal was sought and recorded.ResultsApproximately half of all requests for PM have been upheld (53.0%) and 1/3 of requests have been declined (32.5%). Of those declined, low risk of contralateral breast cancer versus relatively high risk of systemic relapse were commonly cited as justification for PM refusal (45.7%). A proportion of patients who initiated PM discussion subsequently changed their minds (19.6%), or failed to attend clinic appointments (6.5%). Some patients were deemed medically unfit for complex reconstructive surgery (13%), or were declined on the basis of an apparent cosmetic drive for surgery (6.5%), concerns regarding depression or anxiety (2.2%) and/or if family history could not be substantiated (6.5%).DiscussionMDT meetings facilitate cross-specialty interrogation of requests for PM, minimise unnecessary surgery and restrict PM to those likely to derive maximum benefit.
Andreu Perez J, Leff D, Ip H, et al., 2015, From Wearable Sensors to Smart Implants – Towards Pervasive and Personalised Healthcare, IEEE Transactions on Biomedical Engineering, Vol: 62, Pages: 2750-2762, ISSN: 1558-2531
OBJECTIVE: This article discusses the evolution of pervasive healthcare from its inception for activity recognition using wearable sensors to the future of sensing implant deployment and data processing. METHODS: We provide an overview of some of the past milestones and recent developments, categorised into different generations of pervasive sensing applications for health monitoring. This is followed by a review on recent technological advances that have allowed unobtrusive continuous sensing combined with diverse technologies to reshape the clinical workflow for both acute and chronic disease management. We discuss the opportunities of pervasive health monitoring through data linkages with other health informatics systems including the mining of health records, clinical trial databases, multi-omics data integration and social media. CONCLUSION: Technical advances have supported the evolution of the pervasive health paradigm towards preventative, predictive, personalised and participatory medicine. SIGNIFICANCE: The sensing technologies discussed in this paper and their future evolution will play a key role in realising the goal of sustainable healthcare systems.
Shetty K, Leff DR, Orihuela-Espina F, et al., 2015, Looks can be deceiving: is there value in cognitive assessment of complex surgical skills?, Annual Meeting of the Society-of-Academic-and-Research-Surgery (SARS(, Publisher: WILEY-BLACKWELL, Pages: 43-43, ISSN: 0007-1323
Paggetti G, Leff DR, Orihuela-Espina F, et al., 2014, The role of the posterior parietal cortex in stereopsis and hand-eye coordination during motor task behaviours, Cognitive Processing, Vol: 16, Pages: 177-190, ISSN: 1612-4790
Mobasheri MH, Johnston M, King D, et al., 2014, Smartphone breast applications - What's the evidence?, BREAST, Vol: 23, Pages: 683-689, ISSN: 0960-9776
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- Citations: 83
Chang TP, Palazzo F, Flora R, et al., 2014, Imaging parathyroid glands using confocal endomicroscopy: towards real- time intraoperative identification of parathryoid adenoma, Annual Meeting of the Society-of-Academic-and-Research-Surgery, Publisher: WILEY-BLACKWELL, Pages: 3-3, ISSN: 0007-1323
Leff DR, Petrou G, Mavroveli S, et al., 2013, Improving training in breast surgical oncology: The development and preliminary validation of a simulator for wide local excision, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Leibrandt KL, Wisanuvej P, Lin JL, et al., 2013, Classification of safe and erroneous surgery using visual gaze behaviour and cortical brain function, 19th Annual Meeting of the Organization for Human Brain Mapping, Publisher: Science Navigation Group
Jayia P, Oberg E, Tuffaha H, et al., 2013, Should We Manage All Cases of Granulomatous Mastitis Conservatively? A 14 year Experience, BREAST JOURNAL, Vol: 19, Pages: 215-216, ISSN: 1075-122X
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- Citations: 5
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