The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making.

BACKGROUND: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. METHODS: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. RESULTS: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. DISCUSSION: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.

The NeST (neoadjuvant systemic therapy in breast cancer) study - Protocol for a prospective multi-centre cohort study to assess the current utilization and short-term outcomes of neoadjuvant systemic therapies in breast cancer.

INTRODUCTION: Neoadjuvant systemic therapy (NST) has several potential advantages in the treatment of breast cancer. However, there is currently considerable variation in NST use across the UK. The NeST study is a national, prospective, multicentre cohort study that will investigate current patterns of care with respect to NST in the UK. METHODS AND ANALYSIS: Phase 1 - a national practice questionnaire (NPQ) to survey current practice.Phase 2 - a multi-centre prospective cohort study of breast cancer patients, undergoing NST.Women undergoing NST as their MDT recommended primary breast cancer treatment between December 2017 and May 2018 will be included. The breast surgery and oncological professional associations and the trainee research collaborative networks will encourage participation by all breast cancer centres.Patient demographics, radiological, oncological, surgical and pathological data will be collected, including complications and the need for further intervention/treatment. Data will be collated to establish current practice in the UK, regarding NST usage and variability of access and provision of these therapies. Prospective data on 600 patients from ~50 centres are anticipated.Trial registration: ISRCTN11160072. ETHICS AND DISSEMINATION: Research ethics approval is not required for this study, as per the online Health Research Authority decision tool. The information obtained will provide valuable insights to help patients make informed decisions about their treatment. These data should establish current practice in the UK concerning NST, inform future service delivery as well as identifying further research questions.This protocol will be disseminated through the Mammary Fold Academic Research Collaborative (MFAC), the Reconstructive Surgery Trials Network and the Association of Breast Surgery. Participating units will have access to their own data and collective results will be presented at relevant conferences and published in appropriate peer-reviewed journals, as well as being made accessible to relevant patient groups.

Outcomes of Sacral Nerve Stimulation For Faecal Incontinence in Northern Ireland.

BACKGROUND: Sacral nerve root stimulation (SNS) is an effective and developing therapy for faecal incontinence, a debilitating condition that can result in social and personal incapacitation. OBJECTIVES: The objectives of this study are to assess the morbidity of the procedure, improvement in the incontinence scores and Quality of Life (QoL) following SNS. MATERIALS AND METHODS: Patients were identified from the Northern Ireland regional SNS service from 2006 to 2012. Numbers of patients who had temporary placement and permanent placement were collated. Pre and postoperative assessment of severity of incontinence and QoL was performed using Cleveland Clinic Incontinence Score (CCIS) and Short Form-36 (SF-36) respectively. Statistical analysis was undertaken using Wilcoxon signed rank test. Morbidity was assessed by retrospective review of patient records. RESULTS: Seventy-five patients were considered for trial of a temporary SNS. Sixty-one proceeded to insertion of a temporary SNS and, of these, 40 elected to have a permanent SNS. There was a significant reduction in the pre-SNS and post-SNS Cleveland Clinic Incontinence Scores from median of 14 to 9 respectively (p=0.008). There was a significant improvement in Role Physical (p=0.017), General Health (p=0.02), Vitality (p=0.043), Social Functioning (p=0.004), Role Emotional (p=0.007), Mental Health (p=0.013) and Mental Health Summary (p=0.003). However, this is not reflected in the bodily pain and physical functional domains. CONCLUSION: Permanent sacral nerve stimulation is effective and results in significant improvement of faecal incontinence scores and quality of life.

Haemoperitoneum secondary to intrahepatic gallbladder perforation.

A 70-year-old man presented to the accident and emergency department with a 1-day history of right upper quadrant pain and nausea. Examination revealed mild tenderness in the right upper quadrant but no evidence of peritonism or haemodynamic instability. The patient was admitted to the general surgical ward with a diagnosis of cholecystitis and remained stable overnight. In the morning, he developed acute severe pain in the upper abdomen. Examination found him to be tachycardic, tachypnoeic and to have peritonism in the upper abdomen. An urgent CT scan demonstrated cholecystitis but also a small amount of fluid in the pelvis, with Hounsfield units suggestive of blood. The patient proceeded to laparotomy and was found to have massive haemoperitoneum secondary to intrahepatic gallbladder perforation causing liver capsule tear. Cholecystectomy was performed and the liver packed until haemostasis was achieved. The patient made an uneventful recovery.

Well-differentiated papillary mesothelioma: peritoneal implants are not always metastases in the presence of cancer.

INTRODUCTION: Well-differentiated papillary mesothelioma is a rare condition that can cause diagnostic uncertainty. Its appearance resembles metastatic deposits and in the presence of a known primary can often be confused for such. CASE PRESENTATION: In this case, we present a patient who had WDPM in the presence of gastric cancer and emphasise the difficulties in making the diagnosis. CONCLUSION: We highlight the need for a high index of suspicion, biopsies at staging laparoscopy and undertake a review of the literature regarding this uncommon condition.

Skin-reducing mastectomy and one-stage implant reconstruction with a myodermal flap: a safe and effective technique in risk-reducing and therapeutic mastectomy.

INTRODUCTION: Immediate reconstruction following mastectomy for breast cancer has been shown to be oncologically safe and associated with improved psychosocial outcomes for patients. Bostwick described a technique for one-stage implant based reconstruction, combining skin-sparing mastectomy with concurrent reduction of the skin envelope. This report reviews the experience of a single centre using skin-reducing mastectomy and one-stage implant reconstruction in both early stage breast cancer and risk-reducing mastectomy, with specific reference to frequency of complications, implant loss and oncological outcomes. METHODS AND RESULTS: A retrospective review was undertaken to identify women who had undergone skin-reducing mastectomy and one-stage implant reconstruction using a de-epithelialised dermal flap, between October 2008 and October 2012. One hundred and four consecutive mastectomies, with reconstruction, were performed by two surgeons on 64 patients. No complications were seen in 43.8% of patients. At three months, four implants were lost (3.8% of breast reconstructions, 6.3% of patients), due to either peri-implant infection or mastectomy skin flap necrosis. One patient required unplanned return to theatre for evacuation of a haematoma. Minor mastectomy skin flap necrosis was seen in 10 breasts (9.6% of reconstructed breasts) and superficial wound infection in 8 breasts (7.7% of reconstructed breasts). All of these complications were managed conservatively and none required operative intervention. At a median follow up of 35 months (4-53 months) there had been one episode of ipsilateral axillary nodal recurrence. CONCLUSION: One-stage implant reconstruction using a myo-dermal flap technique following skin-reducing mastectomy is safe and should be considered in selected patients. Most complications are minor and will resolve with conservative management. Major complications such as implant failure or immediate reoperation, were relatively uncommon (6.3% patients, 3.8% of reconstructed breasts). Early follow-up suggests that oncological outcomes are satisfactory, but longer follow-up is required to substantiate this.

Ambulatory laparoscopic cholecystectomy outcomes.

BACKGROUND: Outpatient laparoscopic cholecystectomy is an established practice in the United States, but it is not well established in the United Kingdom, and evidence of experience is scarce. The aim of this study was to evaluate the effect of ambulatory laparoscopic cholecystectomy on postoperative morbidity and possible cost savings. We tried to elucidate possible predictors of unplanned admission and readmission rates after discharge. METHODS: This study was conducted in 2 phases. The first phase involved 112 patients and was a retrospective analysis from January 2002 to July 2003 (19 months). The second was a prospective study involving 86 patients from August 2003 to April 2005 (21 months). Consultants, associate specialists, or higher surgical trainees performed the surgeries in a dedicated outpatient procedure unit. The study ended 6 weeks after the operation. RESULTS: Hospital mortality was zero. Overall, 29 (15%) patients required unplanned admissions. Three (1.5%) patients required conversion to open cholecystectomy. Other causes included simple observations (7), wound pain (6), nausea and vomiting (6), suction drain (2), urinary retention (2), operation in the afternoon (2), and shoulder pain (1). Of the patients discharged, 7 (3.5%) required readmission after the initial discharge. Five of the 7 readmissions were wound related and treated conservatively. Two patients underwent laparotomy. CONCLUSION: Ambulatory laparoscopic cholecystectomy appears to be safe, feasible, and cost-effective with a low conversion rate. The unplanned admission rate can be reduced by better training, criteria for discharge, and improvement in anesthesia. This will have implications for surgical training and healthcare resources.

Connected and disconnected support: the impact on the caregiving process in Alzheimer's disease.

The findings of this grounded theory study of Eastern Canadian family caregiving for persons with Alzheimer's disease (AD) provide additional evidence that the presence of both formal and informal social support often fails to make caregiving easier. At family, community, and professional levels, caregiver perception of the helpfulness of support in meeting needs emerged as the indicator of whether support is connected or disconnected. In this paper, we demonstrate and discuss the impact of connected and disconnected support on caregiver progression on the continuum from intimacy to alienation in the process of becoming strangers, the basic social process identified in the study. Implications for further research and practice are discussed.

RBF principal manifolds for process monitoring.

This paper describes a novel means for creating a nonlinear extension of principal component analysis (PCA) using radial basis function (RBF) networks. This algorithm comprises two distinct stages: projection and self-consistency. The projection stage contains a single network, trained to project data from a high- to a low-dimensional space. Training requires solution of a generalized eigenvector equation. The second stage, trained using a novel hybrid nonlinear optimization algorithm, then performs the inverse transformation. Issues relating to the practical implementation of the procedure are discussed, and the algorithm is demonstrated on a nonlinear test problem. An example of the application of the algorithm to data from a benchmark simulation of an industrial overheads condenser and reflux drum rig is also included. This shows the usefulness of the procedure in detecting and isolating both sensor and process faults. Pointers for future research in this area are also given.

Nonlinear control structures based on embedded neural system models.

This paper investigates in detail the possible application of neural networks to the modeling and adaptive control of nonlinear systems. Nonlinear neural-network-based plant modeling is first discussed, based on the approximation capabilities of the multilayer perceptron. A structure is then proposed to utilize feedforward networks within a direct model reference adaptive control strategy. The difficulties involved in training this network, embedded within the closed-loop are discussed and a novel neural-network-based sensitivity modeling approach proposed to allow for the backpropagation of errors through the plant to the neural controller. Finally, a novel nonlinear internal model control (IMC) strategy is suggested, that utilizes a nonlinear neural model of the plant to generate parameter estimates over the nonlinear operating region for an adaptive linear internal model, without the problems associated with recursive parameter identification algorithms. Unlike other neural IMC approaches the linear control law can then be readily designed. A continuous stirred tank reactor was chosen as a realistic nonlinear case study for the techniques discussed in the paper.

Fast parallel off-line training of multilayer perceptrons.

Various approaches to the parallel implementation of second-order gradient-based multilayer perceptron training algorithms are described. Two main classes of algorithm are defined involving Hessian and conjugate gradient-based methods. The limited- and full-memory Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithms are selected as representative examples and used to show that the step size and gradient calculations are critical components. For larger problems the matrix calculations in the full-memory algorithm are also significant. Various strategies are considered for parallelization, the best of which is implemented on parallel virtual machine (PVM) and transputer-based architectures. Results from a range of problems are used to demonstrate the performance achievable with each architecture. The transputer implementation is found to give excellent speed-ups but the problem size is limited by memory constraints. The speed-ups achievable with the PVM implementation are much poorer because of inefficient communication, but memory is not a difficulty.

A neural network regulator for turbogenerators.

A neural network (NN) based regulator for nonlinear, multivariable turbogenerator control is presented. A hierarchical architecture of an NN is proposed for regulator design, consisting of two subnetworks which are used for input-output (I-O) mapping and control, respectively, based on the back-propagation (BP) algorithm. The regulator has the flexibility for accepting more sensory information to cater to multi-input, multioutput systems. Its operation does not require a reference model or inverse system model and it can produce more acceptable control signals than are obtained by using sign of plant errors during training I-O mapping of turbogenerator systems using NNs has been investigated and the regulator has been implemented on a complex turbogenerator system model. Simulation results show satisfactory control performance and illustrate the potential of the NN regulator in comparison with an existing adaptive controller.