Search

Neurofibromatosis type 1 (NF-1)—also commonly known as Von Recklinghausen’s disease—is an autosomal dominant disease that represents a constellation of clinical features. There are well-established links between NF-1 and many tumors; however, the link between NF-1 and breast cancer has more recently been elucidated. While the management of breast cancer is generally well established, there are unique challenges noted in patients with NF-1. There may be delayed presentations due to difficulty in differentiating underlying neurofibroma from a sinister breast mass. Additionally, multiple skin lesions seen in NF-1 create challenges in the interpretation of mammography. Furthermore, a surgical conundrum is created, as these patients appear to have a higher risk of angiosarcoma following radiotherapy. A mastectomy may be the best option as it obviates the need for radiation therapy and ongoing surveillance. A case exemplifying these dilemmas and a review of the literature are presented.

The introduction of breast conservation surgery together with advances in oncoplastic techniques has revolutionized the management of retroareolar breast tumours. Traditionally, cancers in this location were often managed with central excision and primary closure or mastectomy. More recently, oncoplastic breast-conserving techniques such as the Grisotti mammoplasty have been increasingly encouraged as an alternative option as it allows oncological safe margin resections while restoring cosmesis. The use of a Grisotti flap enables safe resection of a retroareolar tumour with concurrent reconstruction of the defect using a local rotational advancement dermoglandular flap allowing a satisfactory cosmetic result in term of contour and projection. This technique is often limited to those patients with sufficient native nipple-inferior mammary fold (IMF) distance to accommodate for some inevitable post-operative reduction in this distance. We describe a modification of the original description, such that satisfactory cosmetic outcome can be achieved, even in patients with a short nipple areolar complex to inframammary fold distance.

BACKGROUND Prevention of depression is a priority to reduce its global disease burden. Targeting specific risk factors, such as rumination, may improve prevention. Rumination-focused Cognitive Behavioral Therapy (RFCBT) was developed to specifically target depressive rumination. OBJECTIVE The primary objective of this study was to test whether guided Web-based RFCBT (i-RFCBT) would prevent the incidence of major depression relative to usual care in UK university students. The secondary objective was to test the feasibility and estimated effect sizes of unguided i-RFCBT. METHODS To address the primary objective, a phase III randomized controlled trial was designed and powered to compare high risk university students (N=235), selected with elevated worry/rumination, recruited via an open access website in response to circulars within universities and internet advertisements, randomized to receive either guided i-RFCBT (interactive Web-based RFCBT, supported by asynchronous written Web-based support from qualified therapists) or usual care control. To address the secondary objective, participants were also randomized to an adjunct arm of unguided (self-administered) i-RFCBT. The primary outcome was the onset of a major depressive episode over 15 months, assessed with structured diagnostic interviews at 3 (postintervention), 6, and 15 months post randomization, conducted by telephone, blind to the condition. Secondary outcomes of symptoms of depression and anxiety and levels of worry and rumination were self-assessed through questionnaires at baseline and the same follow-up intervals. RESULTS Participants were randomized to guided i-RFCBT (n=82), unguided i-RFCBT (n=76), or usual care (n=77). Guided i-RFCBT reduced the risk of depression by 34% relative to usual care (hazard ratio [HR] 0.66, 95% CI 0.35 to 1.25; P=.20). Participants with higher levels of baseline stress benefited most from the intervention (HR 0.43, 95% CI 0.21 to 0.87; P=.02). Significant improvements in rumination, worry, and depressive symptoms were found in the short-to-medium term. Of the 6 modules, guided participants completed a mean of 3.46 modules (SD 2.25), with 46% (38/82) being compliant (completing ≥4 modules). Similar effect sizes and compliance rates were found for unguided i-RFCBT. CONCLUSIONS Guided i-RFCBT can reduce the onset of depression in high-risk young people reporting high levels of worry/rumination and stress. The feasibility study argues for formally testing unguided i-RFCBT for prevention: if the observed effect sizes are robustly replicated in a phase III trial, it has potential as a scalable prevention intervention. CLINICALTRIAL ISRCTN Registry ISRCTN12683436; https://www.isrctn.com/ISRCTN12683436 (Archived by WebCite at http://www.webcitation.org/77fqycyBX) INTERNATIONAL REGISTERED REPOR RR2-10.1186/s13063-015-1128-9

Major depression is a major global health challenge (Collins et al., Nature 475(7354):27–30, 2011). Although interventions for depression are effective, only approximately 1/3 of patients remit and have sustained recovery. Research therefore needs to investigate mechanisms that contribute to vulnerability to relapse/recurrence and to the long-term efficacy of interventions. We hypothesize that considering key depressogenic behaviours as habits informs this issue and review data pertinent to this, considering specific examples of rumination-as-a-mental-habit (Watkins & Nolen-Hoeksema, Journal of Abnormal Psychology 123(1):24–34, 2014) and healthy and unhealthy lifestyle habits relevant to depression.

Background Depression is a global health challenge. Prevention is highlighted as a priority to reduce its prevalence. Although effective preventive interventions exist, the efficacy and coverage can be improved. One proposed means to increase efficacy is by using interventions to target specific risk factors, such as rumination. Rumination-focused CBT (RFCBT) was developed to specifically target depressive rumination and reduces acute depressive symptoms and relapse for patients with residual depression in a randomised controlled trial. Preliminary findings from a Dutch randomised prevention trial in 251 high-risk 15- to 22-year-old subjects selected with elevated worry and rumination found that both supported internet-RFBCT and group-delivered RFCBT equally reduced depressive symptoms and the onset of depressive cases over a period of 1 year, relative to the no-intervention control. Methods/Design A phase III randomised controlled trial following the Medical Research Council (MRC) Complex Interventions Framework will extend a Dutch trial to the United Kingdom, with the addition of diagnostic interviews, primarily to test whether guided internet-RFCBT reduces the onset of depression relative to a no-intervention control. High-risk young adults (aged 18 to 24 years), selected with elevated worry/rumination and recruited through university and internet advertisement, will be randomised to receive either guided internet-RFCBT, supported by clinical psychologists or mental health paraprofessionals, or a no-intervention control. As an adjunct arm, participants are also randomised to unguided internet-RFCBT self-help to provide an initial test of the feasibility and effect size of this intervention. While participants are also randomised to unguided internet-RFCBT, the trial was designed and powered as a phase III trial comparing guided internet-RFCBT versus a no-intervention control. In the comparison between these two arms, the primary outcomes are as follows: a) onset of major depressive episode over a 12-month period, assessed with a Structured Clinical Interview for Diagnosis at 3 months (post-intervention), 6 months and 15 months after randomisation. The following secondary outcomes will be recorded: the incidence of generalized anxiety disorder, symptoms of depression and anxiety, and levels of worry and rumination, measured at baseline and at the same follow-up intervals. In relation to the pilot investigation of unguided internet-RFCBT (the adjunct intervention arm), we will assess the feasibility and acceptability of the data-collection procedures, levels of attrition, effect size and acceptability of the unguided internet-RFCBT intervention. Discussion Widespread implementation is necessary for effective prevention, suggesting that the internet may be a valuable mode of delivery. Previous research suggests that guided internet-RFCBT reduces incidence rates relative to controls. We are also interested in developing and evaluating an unguided version to potentially increase the availability and reduce the costs. Trial Registration Current Controlled Trials ISRCTN12683436. Date of registration: 27 October 2014 Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1128-9) contains supplementary material, which is available to authorized users.

Building on recent work which has investigated social influences on memory and remembering, the present experiment examined the effects of social pressure and confederate confidence on the accuracy and confidence of eyewitnesses. Sixty undergraduate participants watched a video of a staged mugging and then answered questions about the video out loud in the presence of either one or three confederates who had also watched the film with them. Unbeknownst to the participant, the confederate(s) always gave incorrect responses to four out of the eight questions. Participants and confederates were also asked to give confidence scores out loud for each of their answers. Again, unbeknownst to the participant, the confederate(s) always expressed either high or low confidence scores for the incorrect information, depending on condition. Participants gave fewer correct answers, and were less confident, in the presence of three, as opposed to one, confederates. Participants were also more confident, yet no more accurate, when the confederate(s) gave high, as opposed to low, confidence scores. Thus the presumed independence of evidence given by multiple witnesses cannot be safely assumed.

Objectives RRMS is an immune-mediated, demyelinating condition often treated with the monoclonal antibody natalizumab. The administration of this intravenous infusion 4 weekly and the potential for adverse events poses a great inconvenience to patients requiring them to attend hospital day-units to receive treatment. We aimed to establish a safe, patient centric home infusion service for patients being treated with natalizumab as monotherapy for RRMS. Establishment of the home infusion service addressed regulatory requirements, risk minimisation strategies for known toxicities, occupational health and safety concerns and medication management, including storage and transport. Methods An accredited, hospital substitute service (chemo@home) developed a protocol for the administration of natalizumab at home. The protocol was approved by the health services Expert Reference Group (Neurology) and Medication Advisory Group. Medical governance is retained by the neurologist. All health professionals (medical, nursing and pharmacy) complete the relevant sections of the Tysabri Australian prescribing program (TAPP). JC virus seronegative patients are monitored 6 monthly for seroconversion. Resources for the management of adverse reactions (including resuscitation equipment/medications) are available. All pre-infusion regulatory and clinical requirements are fulfilled. Natalizumab infusions are prepared, using a closed system, and administered in the patient’s home by registered nurses. Patient questionnaires on the experience were collected. Results Between February 2014 and January 2017, 34 patients received 494 doses of natalizumab at home. A median of 11 (range 1–37). infusions were given. There were no episodes of anaphylaxis, hypersensitivity, unexpected toxicities and no additional safety concerns identified. Patient satisfaction was high. The at-home service made treatment significantly easier and less stressful than in hospital. Conclusions To our knowledge this is the first establishment of an accredited, hospital-substitute service (chemo@home) in Australia which gives RRMS patients access to natalizumab treatment at home. It was achieved without compromising safety and with a high level of patient satisfaction.

s / International Journal of Surgery 10 (2012) S1–S52 S15 ABSTRACTS 1127: INTRA-OPERATIVE RE-EXCISION OF MARGINS IN BREASTCONSERVING SURGERY: HOW WELL ARE WE ABLE TO JUDGE TUMOUR PROXIMITY? Lorna Cook, Debasish Debnath, Zoe Lin, Raouf Daoud, Isabella Karat, Ian Laidlaw. Frimley Park Hospital, Frimley, UK Introduction: In breast-conserving surgery (BCS), specimen margin involvement with tumour often necessitates re-operation. For this reason, extra margins are often taken at the time of primary operation. The aim of this study was to determine how often such re-excisions are appropriate. Methods: The records of 100 consecutive patients undergoing BCS for cancer during 2011 were analysed. Data was collected on demographics, tumours characteristics, surgery performed and final histology. Results: All 100 patients were female, median age 56 years (range 33-83 years). 66% had intra-operative re-excision of margins. In 26/66 (40%), re-excision was the correct decision. 25 of the 34 patients who had no extramargins taken at all were managed appropriately with the remaining 9 patients having close/positive margins. Unnecessary re-excisions were performed in 40/66 patients. The correct intraoperative decision was therefore made in 51% of patients. Conclusion: The decision regarding intra-operative margin re-excision was appropriate in just over half of all cases and a second operation was avoided in 26%. However, in order to preserve as much uninvolved breast tissue as possible, further work should be done on methods to improve accuracy and to determine whether there are any patient, radiological or pathological predictors to guide intra-operative re-excision. 1181: FACTORS PREDICTING POSITIVE MARGIN STATUS IN BREAST CANCER PATIENTS UNDERGOING BREAST CONSERVING SURGERY Euan Harris , Andrew Lee . University of Dundee, Dundee, Tayside, UK; Abertawe Bro Morgannwg University Healthboard, Swansea, West

Introduction Involved margins in breast-conserving surgery (BCS) are associated with increased risk of local recurrence. In our institution, it is our practice to remove extra adjacent margins of tissue at the time of primary operation if the surgeon feels that tumour excision is incomplete. The aim of this study was to determine the proportion of necessary versus unnecessary intra-operative extra margin excisions and to determine whether there is any patient or pathological factors associated with making a correct decision. Methods Retrospective study of patient records and pathology reports, for 100 consecutive patients undergoing BCS for primary breast cancer at our institution, from 2011-2012. Statistical analysis was performed using Student’s t-test, chi-squared test and a logistic regression model. Results 66% of all patients had extra tissue removed for suspected involved or close margins. The decision to take extra tissue was correct in 48%. As a result, further surgery was prevented in 53% of these patients. Appropriate extra margin excision was significantly associated with younger patient age (P Conclusions Removing the entire tumour with adequate margins in BCS prevents subjecting a patient to further surgery. Conversely, unnecessarily removing uninvolved extra tissue at primary operation in an attempt to prevent re-operation, may impact negatively on breast cosmesis and increases the workload for the Pathologist. This study suggests that older patients, those with small tumours and invasive as opposed to in situ disease are more likely to have extra margins removed unnecessarily. Larger scale studies may help to clarify how we can select patients more accurately for intra-operative margin excision. Disclosure All authors have declared no conflicts of interest.

Objective To determine the identification and the percentage of the false negative of the sentinel nodes in patients with early breast cancer Hospital La Linea, during the period 2007 to 2010. Methods We collect fifty patients with early breast cancer, without clinical and ultrasonographic involvement of axillary nodes, from November 2007 to September 2010. We use the vital dye in the first twenty patients, and the combined technique with vital dye and albumin labeled with technetium 99 in the other thirty patients. The site of injection for patients who use blue dye was the subdermal near to the tumor, and to the patients who use the technetium was the periareolar technique. The sentinel node biopsy was examined during the surgery. The sentinel node was cut through its long axis and then with fine cuts of 250 microns, with freezing technique. The axillary dissection was completed in the first seventeen patients, and in the remaining patients we performed total axillary dissection if the sentinel node was positive for metastasis. Results Sentinel nodes were identified in 49 of 50 patients (98%), procedures. The only case where we did not identify the sentinel node was a patient in the combined technique. The percentage of nodes identified in the patients with vital dye was one sentinel node, and in the patients who use technetium the percentage was two sentinel nodes. The false negative rate was 8% (4 patients), in three of them we found a micrometastasis in the final examination, in the other one we found a macrometastasis. This cases of false negative in the sentinel node biopsy occurred at the beginning of the study. Pathologists acquired a learning curve for sentinel node examination, and practiced subsequently fine cuts in the intraoperative examination of the sentinel node. Conclusion This experience indicates that intraoperative examination of sentinel node biopsy is crucial for staging of the axilla. The rate of identification of sentinel node is excellent and with the use of the technetium the technique is more accurate. The improvement in the learning curve about the intraoperative examination of the sentinel node biopsy has decreased our rates of false negatives. Disclosure All authors have declared no conflicts of interest.