Exploration of chest wall perforator vascular anatomy on standard breast MRI: A potential aid to chest wall perforator flap planning.

Local chest wall perforator flaps (CWPFs) are a volume replacement technique permitting breast-conserving surgery in patients who otherwise may require a mastectomy. These flaps are based on one or more perforating arteries arising from the lateral chest wall that travel through the soft tissue and into the sub-dermal plexus to perfuse the flap. Examples include the lateral intercostal and lateral thoracic artery perforators (LICAP and LTAP, respectively). Cross-sectional imaging of perforating vessels is not routinely performed, and vessels are mapped pre- and peri-operatively using a hand-held acoustic doppler device. As many breast cancer patients undergo pre-operative MRI scanning for oncological purposes, we investigated the role of MRI in mapping the vascular anatomy to aid with the surgical planning of CWPFs. We collated data retrospectively on a cohort of breast cancer patients who underwent breast MRI as part of routine pre-operative imaging. Axial 3D high-resolution dynamic contrast-enhanced MRI sequences with multiplanar reconstructions were analysed by a consultant radiologist. The presence and calibre of lateral chest wall perforator vessels were assessed. Fifty patients were suitable for inclusion. A consistent pattern of lateral chest wall vasculature was observed. Forty-eight patients (96%) demonstrated a bilateral lateral thoracic artery (LTA) descending inferiorly along the chest wall with two-thirds of these communicating with perforating intercostal vessels. True independent LICAP vessels were identified in six patients. From our observations, lateral CWPFs are dependent on an intricate intercommunication between intercostal vessels and the LTA which in turn supply perforators to the lateral chest wall donor site.

Three-dimensional simulation of aesthetic outcome from breast-conserving surgery compared with viewing photographs or standard care: randomized clinical trial.

INTRODUCTION: Over half of women with surgically managed breast cancer in the UK undergo breast-conserving treatment (BCT). While photographs are shown prior to reconstructive surgery or complex oncoplastic procedures, standard practice prior to breast conservation is to simply describe the likely aesthetic changes. Patients have expressed the desire for more personalized information about likely appearance after surgery. The hypothesis was that viewing a three-dimensional (3D) simulation improves patients' confidence in knowing their likely aesthetic outcome after surgery. METHODS: A randomized, controlled trial of 117 women planning unilateral BCT was undertaken. The randomization was three-way: standard of care (verbal description alone, control group), viewing two-dimensional (2D) photographs, or viewing a 3D simulation before surgery. The primary endpoint was the comparison between groups' median answer on a visual analogue scale (VAS) for the question administered before surgery: 'How confident are you that you know how your breasts are likely to look after treatment?' RESULTS: The median VAS in the control group was 5.2 (i.q.r. 2.6-7.8); 8.0 (i.q.r. 5.7-8.7) for 2D photography, and 8.9 (i.q.r. 8.2-9.5) for 3D simulation. There was a significant difference between groups (P < 0.010) with post-hoc pairwise comparisons demonstrating a statistically significant difference between 3D simulation and both standard care and viewing 2D photographs (P < 0.010 and P = 0.012, respectively). CONCLUSION: This RCT has demonstrated that women who viewed an individualized 3D simulation of likely aesthetic outcome for BCT were more confident going into surgery than those who received standard care or who were shown 2D photographs of other women. The impact on longer-term satisfaction with outcome remains to be determined.Registration number: NCT03250260 (http://www.clinicaltrials.gov).

Most women with breast cancer are able to have an operation to remove the cancer while preserving the breast ('lumpectomy'). Whilst cancer control is the most important goal, appearance after surgery has been shown to affect long-term quality of life and is considered when planning treatment. Currently, surgeons simply describe the likely changes in appearance and, for more complex procedures, photographs of other women are shown. Patients themselves have indicated they would like more information regarding the likely changes to their breast after treatment. The authors have developed a way to simulate appearance following lumpectomy and radiotherapy using three-dimensional (3D) photographs. The study invited women undergoing lumpectomy to be assigned at random to one of three groups receiving standard care (discussion), a two-dimensional photograph, or the 3D simulation before their operation. The authors have demonstrated that showing a woman her simulation prior to surgery improves confidence going into treatment.

Development of an online research platform for use in a large-scale multicentre study.

BACKGROUND: Participation in research can be beneficial for patients and healthcare providers, but may prove demanding at patient, clinician and organizational levels. Patient representatives are supportive of online research to overcome these challenges. The aim of this pilot study was to develop an online recruitment platform and test its feasibility and acceptability while evaluating the accuracy of participant-reported data. METHODS: The online research platform was developed in a 1-day 'hackathon' with a digital design company. Women who underwent implant-based breast reconstruction in 2011-2016 were invited by letter containing the web address (URL) of the study site and their unique study number. Once online, participants learned about the study, consented, entered data on demographics, treatment received and patient-reported outcome measures (BREAST-Q™), and booked an appointment for a single hospital visit for three-dimensional surface imaging (3D-SI). Real-time process evaluation was performed. The primary endpoint was recruitment rate. RESULTS: The recruitment rate was 40 per cent. Of the 100 women, 50 logged on to the platform and 40 completed the process through to 3D-SI. The majority of discontinuations after logging on occurred between consenting and entering demographics (3 women, 6 per cent), and between completing the BREAST-Q and booking an appointment for 3D-SI using the online calendar (3 women, 6 per cent). All women completed the online BREAST-Q™ once started. Participants took a median of 23 minutes to complete the online process. Patient-reported clinical data were accurate in 12 of 13 domains compared with electronic records (95 per cent concordance). Process evaluation demonstrated acceptability. CONCLUSION: The results of this pilot demonstrate the online platform to be acceptable, feasible, and accurate for this population from a single institution. The low-burden design may enable participation from centres with less research support and participants from hard-to-reach groups or dispersed geographical locations, but with online access.

Systematic review of therapeutic nipple-sparing versus skin-sparing mastectomy.

Background: The use of nipple-sparing mastectomy (NSM) is increasing, despite unproven oncological safety in the therapeutic setting. The aim of this systematic review was to determine the safety and efficacy of NSM compared with skin-sparing mastectomy (SSM). Methods: A literature search of all original studies including RCTs, cohort studies and case-control studies comparing women undergoing therapeutic NSM or SSM for breast cancer was undertaken. Primary outcomes were oncological outcomes; secondary outcomes were clinical, aesthetic, patient-reported and quality-of-life outcomes. Data analysis was undertaken to explore the relationship between NSM and SSM, and preselected outcomes. Heterogeneity was assessed using the Cochrane tests. Results: A total of 690 articles were identified, of which 14 were included. There was no statistically significant difference in 5-year disease-free survival and mortality for NSM and SSM groups, where data were available. Local recurrence rates were also similar for NSM and SSM (3·9 versus 3·3 per cent respectively; P = 0·45). NSM had a partial or complete nipple necrosis rate of 15·0 per cent, and a higher complication rate than SSM (22·6 versus 14·0 per cent respectively). The higher overall complication rate was due to the rate of nipple necrosis in the NSM group (15·0 per cent). Conclusion: In carefully selected cases, NSM is a viable choice for women with breast cancer who need to have a mastectomy. More research is needed to help further refine which surgical approaches to NSM optimize outcomes.

Bilateral mammoplasty for cancer: Surgical, oncological and patient-reported outcomes.

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.

Standard wide local excision or bilateral reduction mammoplasty in large-breasted women with small tumours: Surgical and patient-reported outcomes.

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.

Long term results of treatment of breast cancer without axillary surgery - Predicting a SOUND approach?

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.

Determinants of optimal mastectomy skin flap thickness.

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.

Sentinel lymph node biopsy after previous axillary surgery: A review.

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.

Axillary nodal yields: a comparison between primary clearance and completion clearance after sentinel lymph node biopsy in the management of breast cancer.

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.

Nipple-sparing mastectomy.

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.

Development and validation of a model predictive of occult nipple involvement in women undergoing mastectomy.

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.

Squamous cell carcinoma arising in a tall cell papillary carcinoma of the thyroid.

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.

Adenovirus gene transfer causes inflammation in the brain.

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.