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Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer., Competing Interests: The authors declare no conflict of interest.

Purpose: Access to nuclear medicine department for sentinel node imaging remains an issue in number of hospitals in the UK and many parts of the world. Sentinella ® is a portable imaging camera used intra-operatively to produce real time visual localisation of sentinel lymph nodes., Methods: Sentinella ® was tested in a controlled laboratory environment at our centre and we report our experience on the first use of this technology from UK. Moreover, preoperative scintigrams of the axilla were obtained in 144 patients undergoing sentinel node biopsy using conventional gamma camera. Sentinella ® scans were done intra-operatively to correlate with the pre-operative scintigram and to determine presence of any residual hot node after the axilla was deemed to be clear based on the silence of the hand held gamma probe., Results: Sentinella ® detected significantly more nodes compared with CGC (p < 0.0001). Sentinella ® picked up extra nodes in 5/144 cases after the axilla was found silent using hand held gamma probe. In 2/144 cases, extra nodes detected by Sentinella ® confirmed presence of tumour cells that led to a complete axillary clearance., Conclusions: Sentinella ® is a reliable technique for intra-operative localisation of radioactive nodes. It provides increased nodal visualisation rates compared to static scintigram imaging and proves to be an important tool for harvesting all hot sentinel nodes. This portable gamma camera can definitely replace the use of conventional lymphoscintigrams saving time and money both for patients and the health system., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aims: We aimed to determine the effectiveness of CK19 mRNA copy number and tumour related factors in predicting non-sentinel axillary nodal involvement, in order to facilitate the formulation of local treatment guidelines for axillary clearance (ANC) following intra-operative analysis of the sentinel node biopsy (SNB) using one-step nucleic acid amplification (OSNA)., Methods: Patients due to have (SNB) at our institution for breast cancer as well as patients with high grade ductal carcinoma in situ with pre-operative negative assessment of the axilla were included. Alternate slices of each node were sent for assessment by either OSNA or histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA nodal copy number, the total tumour load (TTL) measured by summation of mRNA copy numbers of all positive nodes, the nodal status at ANC and tumour characteristics for each patient were recorded. A model of risk probability was constructed using TTL and tumour related factors., Results: 664 nodes were analysed from 425 patients who had SNB performed between 2011 and 2014. ANC was performed on 105 of these patients. The concordance between OSNA and histology was 91.4% and negative predictive value (NPV) was 97%. TTL (p = 0.003) and LVI (p = 0.04) were identified as risk factors for non-sentinel nodal involvement. The risk probability model identified all patients with pN2 disease for ANC., Conclusion: In the future a decision to perform ANC will be based on a risk stratification model based on TTL and tumour related factors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The high incidence and low mortality of breast cancer surgery has led to an increasing emphasis on the cosmetic outcome of surgical treatment. Advances in aesthetic evaluation, as well as surgical planning and outcome prediction, have been investigated by using geometrically precise 3D modelling of the breast surface prior to surgery and after the procedure. However, existing solutions are based on expensive site specific setups and remain weakly validated. In this paper, we explore the possibility of using low-cost RGBD cameras as an affordable and mobile system for breast surface reconstruction. The methodology relies on sensor calibration, uncertainty-driven point filtering, dense reconstruction and subsequent multi-view joint optimization to diffuse residual pose errors. Results from a phantom study, with ground truth obtained through commercially available scanners, indicate that the approach is promising with RMS errors in order of 2 mm. A clinical study shows the practical applicability of our method and compares favourably to high-end scanning solutions.

One step nucleic acid (OSNA) is a molecular diagnostic assay for intra-operative detection of sentinel node metastases. This study compared OSNA with standard histopathology in 283 nodes from 170 patients to evaluate sensitivity, specificity and concordance of the two methods. Additional analysis was done to investigate how cytokeratin 19 mRNA copy number affects prediction of non-sentinel node positivity. OSNA sensitivity was 93.2% and specificity 95.8%. Concordance between OSNA and histology was 95.6%. In the patients who had axillary clearance, the OSNA mRNA copy number on the sentinel node had 100% negative predictive value for histologically proven metastasis. mRNA copy numbers <1400 were not associated with histologically proven metastasis in subsequent nodes at axillary clearance. OSNA is a reliable method for the intra-operative evaluation of axillary lymph node metastasis even when half of the lymph node is used. Identification of mRNA copy number threshold predicting the positivity of non-sentinel axillary nodes seems to be feasible and would be clinically important., (Copyright © 2014. Published by Elsevier Ltd.)

Radioguided surgery has been investigated and applied to almost any neoplastic disease that is surgically treated. The impact of radioguided surgery on the surgical management of cancer patients includes relevant and real-time information to the surgeon regarding the location and extent of the disease, as well as regarding the assessment of surgical resection margins. Despite the fact that sentinel lymph node biopsy has been worldwide accepted as a highly accurate staging method for various solid cancers (among which breast cancer and cutaneous melanoma), some potential intraoperative drawbacks still remain. This article provides an update on currently available perioperative techniques regarding the use of radiotracers for radioguided surgery and sentinel lymph node mapping and biopsy, in particular in combination with vital dyes or other agents. The integration of computer technology and data processing makes it possible to integrate anatomic and functional images together with 3D rendering systems. This facilitates the targeted-tissue perioperative localization, especially in anatomically complex areas. Furthermore, we provide an update on advances in the integration of intraoperative imaging devices as well as optical tracers for the surgical management of patients. Evidence is emerging that these devices, together with new potential tracers, may improve intraoperative identification of sentinel nodes and/or tumors. A detailed presentation on a portable gamma camera in breast cancer patients, and the application of perioperative imaging devices in gynaecological cancers are included. Other important procedures, such as ROLL and RSL for occult lesion excision in the breast and other organs, are extensively discussed.

Intra-operative radiotherapy (IORT) as a treatment for breast cancer is a relatively new technique that is designed to be a replacement for whole breast external beam radiotherapy (EBRT) in selected women suitable for breast-conserving therapy. This article reviews twelve reasons for the use of the technique, with a particular emphasis on targeted intra-operative radiotherapy (TARGIT) which uses X-rays generated from a portable device within the operating theatre immediately after the breast tumour (and surrounding margin of healthy tissue) has been removed. The delivery of a single fraction of radiotherapy directly to the tumour bed at the time of surgery, with the capability of adding EBRT at a later date if required (risk-adaptive technique) is discussed in light of recent results from a large multinational randomised controlled trial comparing TARGIT with EBRT. The technique avoids irradiation of normal tissues such as skin, heart, lungs, ribs and spine, and has been shown to improve cosmetic outcome when compared with EBRT. Beneficial aspects to both institutional and societal economics are discussed, together with evidence demonstrating excellent patient satisfaction and quality of life. There is a discussion of the published evidence regarding the use of IORT twice in the same breast (for new primary cancers) and in patients who would never be considered for EBRT because of their special circumstances (such as the frail, the elderly, or those with collagen vascular disease). Finally, there is a discussion of the role of the TARGIT Academy in developing and sustaining high standards in the use of the technique.

The international randomised targeted intraoperative radiotherapy (TARGIT) trial has demonstrated evidence of non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam(®)) and conventional external beam radiotherapy (EBRT) in women with early breast cancer in terms of the primary outcome measure of risk of local relapse within the treated breast. Cosmesis is an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy contributing to this. It was unknown if the single high dose of TARGIT may lead to damaging fibrosis and thus impair cosmesis further, so we objectively evaluated the aesthetic outcome of patients within the TARGIT randomised controlled trial. We have used an objective assessment tool for evaluation of cosmetic outcome. Frontal digital photographs were taken at baseline (before TARGIT or EBRT) and yearly thereafter for up to 5 years. The photographs were analysed by BCCT.core, a validated software which produces a composite score based on symmetry, colour and scar. 342 patients were assessed, median age at baseline 64 years (IQR 59-68). The scores were dichotomised into Excellent and Good (EG), and Fair and Poor (FP). There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group at year 1 (OR 2.07, 95 % CI 1.12-3.85, p = 0.021) and year 2 (OR 2.11, 95 % CI 1.0-4.45, p = 0.05). Following a totally objective assessment in a randomised setting, the aesthetic outcome of patients demonstrates that those treated with TARGIT have a superior cosmetic result to those patients who received conventional external beam radiotherapy.

Background: Religious/spiritual resources may serve multiple functions in adjustment to cancer. However, there is very little evidence of the importance of religious/spiritual variables outside the USA. This paper reports the cross-sectional data of a longitudinal study examining the beneficial and harmful effects of religious/spiritual coping resources on adjustment in the first year after a breast cancer diagnosis., Method: One hundred and fifty-five patients newly diagnosed with breast cancer were assessed after surgery. Several aspects of religiousness/spirituality in relation to anxiety and depression were examined: religiosity/spirituality, strength of faith, belief in God, private and public practices, spiritual involvement, perceived spiritual support and positive and negative religious coping strategies. Non-religious coping, social support and optimism were also assessed., Results: 'Feeling punished and abandoned by God' significantly explained 5% of the variance in increased levels of anxiety but was partially mediated by denial coping. It was also partially mediated by acceptance coping, lowering levels of anxiety. Feeling punished and abandoned by God was a significant independent predictor of depressed mood, explaining 4% of the variance., Conclusion: Using religious/spiritual resources in the coping process during the early stages of breast cancer may play an important role in the adjustment process in patients with breast cancer. Patients may benefit from having their spiritual needs addressed as experiencing some form of religious/spiritual struggle may serve as a barrier to illness adjustment. Implications for research and clinical practices are discussed., (Copyright © 2012 John Wiley & Sons, Ltd.)

We present the case of an 83 year old woman with a cardiac pacemaker located close in distance to a subsequently diagnosed invasive ductal carcinoma of the left breast. Short range intraoperative radiotherapy was given following wide local excision and sentinel node biopsy. The challenges of using ionising radiation with pacemakers is also discussed.

Purpose: In vivo dosimetry provides an independent check of delivered dose and gives confidence in the introduction or consistency of radiotherapy techniques. Single-fraction intraoperative radiotherapy of the breast can be performed with the Intrabeam compact, mobile 50 kV x-ray source (Carl Zeiss Surgical, Oberkochen, Germany). Thermoluminescent dosimeters (TLDs) can be used to estimate skin doses during these treatments., Methods and Materials: Measurements of skin doses were taken using TLDs for 72 patients over 3 years of clinical treatments. Phantom studies were also undertaken to assess the uncertainties resulting from changes in beam quality and backscatter conditions in vivo., Results: The mean measured skin dose was 2.9 ± 1.6 Gy, with 11% of readings higher than the prescription dose of 6 Gy, but none of these patients showed increased complications. Uncertainties due to beam hardening and backscatter reduction were small compared with overall accuracy., Conclusions: TLDs are a useful and effective method to measure in vivo skin doses in intraoperative radiotherapy and are recommended for the initial validation or any modification to the delivery of this technique. They are also an effective tool to show consistent and safe delivery on a more frequent basis or to determine doses to other critical structures as required., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Currently, there is a lack of data on the role of combined positron emission tomography-computed tomography (PET-CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of (18)F-fluorodeoxyglucose ((18)F-FDG)-PET-CT in this patient population., Methods: We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with (18)F-FDG-PET-CT. All PET-CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained., Results: The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET-CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET-CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery. Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions., Conclusion: Integrated (18)F-FDG-PET-CT may have a role in staging patients presenting with early breast cancer.

Objectives: The use of religious/spiritual coping strategies may be particularly prevalent when dealing with the stress of a cancer diagnosis. There has, however, been very little research conducted on this topic outside the USA. Existing measures of coping largely ignore the complexity of religious/spiritual coping and its potential to be adaptive as well as maladaptive. The aim of this study was to examine the prevalence of various religious coping strategies in a UK cancer sample., Method: A longitudinal design assessed religious coping strategies in patients newly diagnosed with breast cancer at the time of surgery and at 3 and 12 months post surgery. We recruited 202 patients of which, at 12 months, 160 remained. A non-religious coping measure was included for comparison., Results: The use of religious coping strategies was overall common; up to 73% of patients used positive religious coping to some degree at surgery and up to 53% experienced various religious/spiritual struggles. The use of some religious coping strategies showed differing patterns of change across time while others remained stable., Conclusion: Using religious/spiritual resources in the coping process during the early stages of breast cancer appears common in the UK. Patients may benefit from having their spiritual needs addressed as experiencing some form of religious/spiritual struggle may serve as a barrier to illness adjustment. Health-care professionals should also be aware that some religious coping strategies may be more prevalent at different times during the first year of illness., (Copyright © 2010 John Wiley & Sons, Ltd.)

The use of religious/spiritual resources may increase when dealing with the stress of a cancer diagnosis. However, there has been very little research conducted into changes in religious/spiritual beliefs and practices as a result of a cancer diagnosis outside the USA. The aim of this study was to examine the impact of a breast cancer diagnosis on patients' religious/spiritual beliefs and practices in the UK where religious practice is different. The study used two methods. One compared the religious/spiritual beliefs and practices of 202 patients newly diagnosed with breast cancer with those of a control group of healthy women (n = 110). The other examined patients' perceived change in religious/spiritual beliefs and practices at the time of surgery with those in the year prior to surgery. The aspects of religiousness/spirituality assessed were: levels of religiosity/spirituality, strength of faith, belief in God as well as private and public practices. Patient's perceived their belief in God, strength of faith and private religious/spiritual practices to have significantly increased shortly after surgery compared with the year prior to surgery. However, there were no significant differences in religious/spiritual beliefs and practices between patients and healthy participants. Change scores demonstrated both a reduction and an increase in religious/spiritual beliefs and practices. Although belief in God, strength of faith and private religious/spiritual practices were perceived by patients to be significantly higher after their cancer diagnosis, no significant differences in religious/spiritual beliefs and practices were found between the cancer group at the time of surgery and the control group. Different methodologies appear to produce different results and may explain contradictions in past US studies. Limitations of this study are discussed and suggestions for future research are made.

Purpose: External beam radiation therapy (EBRT) following wide local excision of the primary tumor is the standard treatment in early breast cancer. In some circumstances this procedure is not possible or is contraindicated or difficult. The purpose of this study was to determine the safety and efficacy of targeted intraoperative radiotherapy (TARGIT) when EBRT is not feasible., Methods and Materials: We report our experience with TARGIT in three centers (Australia, Germany, and the United Kingdom) between 1999 and 2008. Patients at these centers received a single radiation dose of 20 Gy to the breast tissue in contact with the applicator (or 6 Gy at 1-cm distance), as they could not be given EBRT and were keen to avoid mastectomy., Results: Eighty patients were treated with TARGIT. Reasons for using TARGIT were 21 patients had previously received EBRT, and 31 patients had clinical reasons such as systemic lupus erythematosus, motor neuron disease, Parkinson's disease, ankylosing spondylitis, morbid obesity, and cardiovascular or severe respiratory disease. Three of these patients received percutaneous radiotherapy without surgery; 28 patients were included for compelling personal reasons, usually on compassionate grounds. After a median follow-up of 38 months, only two local recurrences were observed, an annual local recurrence rate of 0.75% (95% confidence interval, 0.09%-2.70%)., Conclusions: While we await the results of the randomized trial (over 2,000 patients have already been recruited), TARGIT is an acceptable option but only in highly selected cases that cannot be recruited in the trial and in whom EBRT is not feasible/possible., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The surgical treatment of early breast cancer has evolved from the removal of the entire breast and surrounding tissues (mastectomy) to the removal of the tumour together with a margin of healthy tissue (lumpectomy). Adjuvant radiotherapy, however, is still mainly given to the whole breast. Furthermore, external beam radiotherapy is often given several months after initial surgery and requires the patient to attend the radiotherapy centre daily for several weeks. A single fraction of radiotherapy given during surgery directly to the tumour bed (intraoperative radiotherapy) avoids these problems. The rationale and level-1 evidence for the safety and efficacy of the technique are reviewed.

Purpose: Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of (18)F-FDG to detect angiogenesis in early breast carcinoma using PET/CT., Methods: Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUV(max)) and mean standardized uptake value (SUV(mean)). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1)., Results: The SUV(max) showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = -0.16, p = 0.496. The SUV(mean) showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = -0.18, p = 0.443, Conclusion: (18)F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, (18)F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease.

Background: Women with breast cancer and a positive axillary sentinel lymph node (SLN) are recommended to undergo complete axillary lymph node dissection; however, further nodal disease is not always present. Mathematical models have been constructed to determine the risk of metastatic disease; three of these were evaluated independently., Methods: Data from 108 women with breast cancer who had a positive SLN biopsy and completion axillary lymph node dissection were used. Measurements of additional parameters over those usually determined (such as size of SLN metastasis) were assessed under the supervision of two pathologists. These data were used to determine the predicted risk of non-SLN metastases using three mathematical models (from Memorial Sloan-Kettering Cancer Center (MSKCC), Cambridge University and Stanford University) and a comparison made with the observed findings. Analyses were made using the area under the receiver operating characteristic (ROC) curve (AUC)., Results: Some 53 (49.1 per cent) of 108 patients had a positive non-sentinel axillary lymph node metastasis. The AUC values were 0.63, 0.72 and 0.67 for the MSKCC, Cambridge and Stanford nomograms respectively., Conclusion: This independent comparison found no significant difference between the models, although the Cambridge model had the advantage of requiring fewer measurements with a more accurate predictive performance., (Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Intraoperative diagnosis of sentinel node metastases enables an immediate decision to proceed to axillary lymph node dissection, avoiding a second operation in node-positive women with breast cancer., Methods: An optical scanner was developed that interrogated the cut surface of bivalved, but otherwise unprocessed, sentinel lymph nodes with pulses of white light by elastic scattering spectroscopy (ESS). The scattered light underwent spectral analysis, and individual spectra were initially correlated with conventional histology to develop a diagnostic algorithm. This algorithm was used to create false colour-coded maps of scans from an independent set of nodes, and the optimal criteria for discriminating between normal and cancer spectra were defined statistically., Results: The discriminant algorithm was developed from a training set of 2989 spectra obtained from 30 metastatic and 331 normal nodes. Subsequent scans from 129 independent nodes were analysed. The scanner detected macrometastases (larger than 2 mm) with a sensitivity of 76 per cent (69 per cent including micrometastases) and specificity of 96 per cent., Conclusion: In this proof-of-principle study, the ESS results were comparable with current intraoperative diagnostic techniques of lymph node assessment., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20x20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.

Introduction: Sentinel lymph node (SLN) biopsy is the evolving standard of care for the management of early breast cancer. Accurate identification of the SLN is paramount for success of this procedure. Various techniques are described for SLN identification, but the superficial injection techniques, advocated by the UK National Training Programme (NEW START), are validated, reproducible and rapid. Pre-operative lymphoscintigraphy provides a road map for the surgeon and requires a reporting template., Methods: As one of the NEW START training institutions in the UK practising this technique, we reviewed a mature series of 100 unselected, consecutive SLN lymphoscintigraphy procedures. We correlated the imaging, operative and pathology findings and have provided technical details of the technique and a template for reporting SLN lymphoscintigrams., Results: The SLN localisation rate was 99% with one failed imaging. Seven patients required delayed imaging. The mean activity of the radiocolloid injected was 14.4MBq (range 8.3-23 MBq). The SLNs were visualised in the ipsilateral axilla in 98 images, intramammary in 3, and internal mammary in 1. A mean of 1.35 nodes were classified as 'True' SLNs on imaging criteria. Intra-operatively, a mean of 1.91 SLNs were excised. 32 of 116 hot and blue nodes, 7 of 15 only blue nodes, 13 of 47 only hot and 7 of 13 parasentinel nodes harboured metastases., Conclusion: The NEW START recommended, combined superficial injection techniques, have high localisation rates. Pre-operative sentinel node imaging is recommended and a template for reporting is provided.

Phyto-oestrogens are plant compounds structurally similar to oestradiol, which have been proposed to have protective effects against breast cancer. The main class of phyto-oestrogens in the Western diet is lignans. Literature reports on the effect of lignans in breast cancer risk have been conflicting. We performed three separate meta-analyses to examine the relationships between (i) plant lignan intake, (ii) enterolignan exposure and (iii) blood enterolactone levels and breast cancer risk. Medline, BIOSIS and EMBASE databases were searched for publications up to 30 September 2008, and 23 studies were included in the random effects meta-analyses. Overall, there was little association between high plant lignan intake and breast cancer risk (11 studies, combined odds ratio (OR): 0.93, 95% confidence interval (95% CI): 0.83-1.03, P=0.15), but this association was subjected to marked heterogeneity (I(2)=44%). Restricting the analysis to post-menopausal women, high levels of plant lignan intake were associated with reduced breast cancer risk (7 studies, combined OR: 0.85, 95% CI: 0.78, 0.93, P<0.001) and heterogeneity was markedly reduced (I(2)=0%). High enterolignan exposure was also associated with breast cancer (5 studies, combined OR: 0.73, 95% CI: 0.57, 0.92, P=0.009) but, again, there was marked heterogeneity (I(2)=63%). No association was found with blood enterolactone levels (combined OR: 0.82, 95% CI: 0.59-1.14, P=0.24). In conclusion, plant lignans may be associated with a small reduction in post-menopausal breast cancer risk, but further studies are required to confirm these results.

Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.

Background: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital., Methods: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash., Results: A total of 18,810 samples were processed, of which 850 (4.5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3.78 beds per year (276,220 pounds sterling), compared with the annual mean for the preceding 6 years. The cost of screening was 302,500 pounds sterling, making a net loss of 26,280 pounds sterling. Compared with 2005, however, there was a net saving of 545,486 pounds sterling., Conclusion: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established., (2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Unlabelled: Intraoperative detection of sentinel node metastases in breast cancer enables immediate axillary lymph node dissection. This approach, however, introduces uncertainty for patients as to the extent of surgery. Waking to find a surgical drain implies more extensive surgery and worse prognosis disease. False negative diagnoses may cause disappointment., Aim: To evaluate patients' views and preferences on intraoperative diagnosis of sentinel nodes in breast cancer., Methods: Questionnaire based survey of 100 patients who had previously undergone sentinel node biopsy with intraoperative diagnosis using touch imprint cytology (TIC). Patients were encouraged to add free text comments., Results: Sixty-four patients responded to the questionnaire. Patients rated the information provided and their understanding of the procedure highly. Fifty-nine percent of respondents overestimated the sensitivity of TIC. Ninety-five percent of patients would choose to undergo intraoperative diagnosis in future if required. Five percent of patients would choose not to undergo intraoperative diagnosis, citing the resultant uncertainty, disappointment on waking and needing time to come in terms with the diagnosis of metastases as reasons., Conclusion: Given the choice, most patients would choose intraoperative diagnosis, though a minority would explicitly not, due to the adverse psychological effect thereof. Despite a good understanding of the procedure, the majority of patients overestimate the sensitivity of intraoperative diagnosis of sentinel nodes, which may heighten disappointment when a false negative diagnosis occurs. Intraoperative diagnosis should not be the automatic choice and patients should be actively involved in this decision making process.

Optimal sentinel node identification requires using the combination technique with blue dye and radiocolloid. Allergic reactions to the common blue dyes in use are well recognised. In this report, we present a patient with breast carcinoma who developed a type I hypersensitivity reaction to intradermal injection of technetium-99m labelled nanocolloidal albumin. While reactions to colloids are rare, and in this case minor, operators using this radiopharmaceutical should be prepared for a potential severe anaphylactic reaction.

Introduction: Axillary lymph node status for lymphatic staging in breast cancer is the best prognostic indicator and guides systemic treatment. Sentinel lymph node (SLN) biopsy is a novel, minimally invasive technique for lymphatic staging proven to improve quality of life. The accurate detection of the SLN is paramount for the success of the procedure., Methods: Relevant literature was reviewed with regards to the different dyes and techniques used for the detection of SLN in breast cancer., Results: Highest identification rates and lowest false negative rates are achieved by using the combined blue dye and radiocolloid technique with pre-operative imaging using a gamma camera. There is a well-recognized learning curve to successfully perform SLN biopsy., Conclusions: The concept of SLN has been well validated and is the standard of care in early breast cancer. A multidisciplinary approach and structured training is the key to the successful introduction of the technique.

The present paper systematically reviews studies examining the potential beneficial or harmful effects of religious/spiritual coping with cancer. Using religion and spirituality as resources in coping may be specifically prevalent in patients with cancer considering the potentially life-threatening nature of the illness. Religious/spiritual coping may also serve multiple functions in long-term adjustment to cancer such as maintaining self-esteem, providing a sense of meaning and purpose, giving emotional comfort and providing a sense of hope. Seventeen papers met the inclusion criteria of which seven found some evidence for the beneficial effect of religious coping, but one of these also found religious coping to be detrimental in a sub-sample of their population. A further three studies found religious coping to be harmful and seven found non-significant results. However, many studies suffered from serious methodological problems, especially in the manner in which religious coping was conceptualised and measured. The studies also failed to control for possible influential variables such as stage of illness and perceived social support. Due to this, any firm conclusions about the possible beneficial or harmful effects of religious coping with cancer is lacking. These problems are discussed and suggestions for future studies are made.

Background: Intraoperative detection of sentinel lymph node (SLN) metastases enables the surgeon to take an immediate decision to proceed to completion axillary lymph node dissection (ALND). The aim of this study was to determine the accuracy of touch imprint cytology (TIC) for the diagnosis of SLN metastases in sentinel nodes from women with breast cancer., Methods: Touch imprints from 235 sentinel nodes in 133 women with breast cancer were diagnosed by cytopathology and compared with definitive histopathology results. After a feasibility study, a real-time study was performed with the surgeon proceeding to ALND based on the TIC diagnosis. The clinical opinion of the operating surgeon as to whether the SLN appeared to contain metastases was recorded, as was the time taken for the result to be available., Results: TIC detected metastases with a sensitivity of 81.1 per cent and a specificity of 100 per cent. False-negative TIC diagnoses were associated with micrometastases and lobular carcinoma. The majority of false-negative diagnoses were due to sampling rather than interpretation errors. Clinical assessment of sentinel nodes had a sensitivity of 64.3 per cent and a specificity of 87.6 per cent., Conclusion: TIC is feasible and enables the rapid diagnosis of SLN metastases with an acceptable accuracy for clinical use in ductal carcinoma of the breast.

Breast cancer is presenting earlier, and treatment is becoming less invasive. We review two recent changes in the approach to management. Sentinel lymph node biopsy is a minimally invasive technique to identify the first draining lymph node in direct communication with the primary tumor; it enables "selective lymphadenectomy." Axillary lymph node dissection is reserved as a therapeutic procedure only for proven node positive patients. The concept has been validated, the techniques have been optimized, and randomized controlled trials have confirmed lower morbidity without compromising regional control compared with conventional treatment. The procedure is considered by many as the standard of care for staging the axilla in early breast cancer, although several unanswered questions remain. Adequate training and experience in the technique are vital to ensure high sentinel node identification and low false negative rates. Intraoperative radiotherapy is an attractive concept that enables delivery of single fraction radiotherapy in the operating room immediately after resection of the primary tumor. It is convenient for patients and appears effective in pilot studies. Partial breast irradiation to the index quadrant has been practiced for many years in the form o brachytherapy. Trials are under way comparing intraoperative radiotherapy with conventional external bea irradiation. Intra-operative radiotherapy should not be used outside of clinical trials until the results of the current randomized trials are known.

Results are presented of a study to monitor the changes in the optical properties of breast tissue over a 12-month period after interstitial laser photocoagulation treatment of a fibroadenoma. The study involved generating cross-sectional images of the breast with a multichannel time-resolved imaging system and a nonlinear image reconstruction algorithm. Images of the internal absorbing and scattering properties revealed the expected initial inflammatory response, followed by the development of low-scattering cysts consistent with corresponding ultrasound examinations. Although results indicate that purely qualitative images can potentially provide clinically valuable data, means of enhancing diagnostic information by overcoming present limitations of the approach are discussed.

Background: Sentinel node biopsy is becoming the staging investigation of choice for early breast cancer. Optimal identification of the sentinel node requires the utilization of a radionuclide in combination with blue dye. Gamma probe guided surgery is a skill that is currently unfamiliar to many surgeons. Appropriate training within the surgical skills laboratory could play a major role in the widespread implementation of this technique, but no suitable model currently exists for this purpose., Aim: To develop a realistic phantom for the teaching and practice of the core new skills required of a surgeon to perform gamma probe guided sentinel node biopsy in breast cancer., Methods: We describe the development of our sentinel node biopsy simulator which consists of a torso with its arm extended in an operating position. The replaceable breast and axilla are constructed from a thermoplastic elastomer gel, which has similar physical and radiation attenuation properties to that of human tissue. Radionuclide injection sites and radioactive sentinel nodes are simulated by hollow blue coloured PVC beads filled with Technetium-99m. The model allows demonstration and practice of injection techniques, imaging techniques and gamma probe guided removal of sentinel nodes., Conclusion: We believe that training for sentinel node biopsy should begin in the surgical skills laboratory. The model we have developed is able to provide an accurate simulation of all new practical skills required for accurate sentinel node identification. It is an important aid to training in the sentinel lymph node biopsy procedure for breast carcinoma.

The ability to provide the best treatment for breast cancer depends on establishing whether or not the cancer has spread to the lymph nodes under the arm. Conventional assessment requires tissue removal, preparation, and expert microscopic interpretation. In this study, elastic scattering spectroscopy (ESS) is used to interrogate excised nodes with pulsed broadband illumination and collection of the backscattered light. Multiple spectra are taken from 139 excised nodes (53 containing cancer) in 68 patients, and spectral analysis is performed using a combination of principal component analysis and linear discriminant analysis to correlate the spectra with conventional histology. The data are divided into training and test sets. In test sets containing spectra from only normal nodes and nodes with complete replacement by cancer, ESS detects the spectra from cancerous nodes with 84% sensitivity and 91% specificity (per-spectrum analysis). In test sets that included normal nodes and nodes with partial as well as complete replacement by cancer, ESS detects the nodes with cancer with an average sensitivity of 75% and specificity of 89% (per-node analysis). These results are comparable to those from conventional touch imprint cytology and frozen section histology, but do not require an expert pathologist for interpretation. With automation of the technique, results could be made available almost instantaneously. ESS is a promising technique for the rapid, accurate, and straightforward detection of metastases in excised sentinel lymph nodes., (Copyright 2004 Society of Photo-Optical Instrumentation Engineers.)

The surgical management of breast cancer has become less invasive in recent years. Accurate lymphatic staging remains crucial for determining adjuvant treatment and prognosis. Sentinel node biopsy enables highly accurate lymphatic staging with minimal morbidity. In this article we give a historical overview, outline the technique, give succinct guidelines for practice based on current evidence, examine recently published work as well as highlight the most important trials in progress. The advent of sentinel node biopsy for the routine treatment of breast carcinoma will have significant implications on the whole team involved in beast cancer care. Training for the entire team needs to be addressed, and preparations made as patients are likely to soon demand this procedure as part of the routine management of their breast carcinoma.

The techniques of lymphatic mapping and sentinel node biopsy are finding increasing utility in the management of the loco-regional lymphatics in many areas of oncology. Our unit is currently investigating their feasibility in relation to the management of the clinically node negative neck in oral squamous cell carcinoma. In order to reduce patient discomfort, and to remove the possibility of sharps injury, particularly in the high-risk patient, we report the use of a needle free device for the intra-oral delivery of the radiopharmaceutical. We believe that this is the first report using such a device in the oral cavity for the purpose of lymphoscintigraphy, and that it has significant advantages over the conventional hypodermic needle in certain patient groups.

The aim of this study was to evaluate the role of dynamic imaging in sentinel lymph node (SLN) biopsy in breast cancer. Patients with T1/T2, N0 invasive breast cancer underwent SLN localisation using intra-dermal injection of 15 MBq of 99mTc-nanocolloid. Gamma camera anterior-oblique dynamic imaging commenced simultaneously with tracer administration for 45 min, and was followed by anterior and lateral static imaging. Dynamic imaging data was reformatted into image files of different time-frames. Patterns of uptake were analysed using the sequences of dynamic frames and time-activity curve (TAC). SLN localisation was successful in 70/73 studies (96%) in 72 patients. Imaging information was present within the first 15 min of dynamic imaging in 67/70 studies (96%). Critical analysis of dynamic data helped to differentiate true SLN from secondary echelon nodes in eight studies and transient foci of radioactivity in six studies. In 17 studies, SLN contained metastatic disease. The detection of SLN metastasis was independent from the use of dynamic imaging. Dynamic imaging improves the interpretation of preoperative SLN imaging for breast cancer, but does not contribute significantly to the successful detection of SLN. Hence, preoperative dynamic imaging is not necessary in SLN biopsy for breast cancer.

The introduction of sentinel-lymph-node biopsy has brought new impetus to the early staging of cancer in general, and breast cancer in particular. This technique has rekindled the discussion on the present role and routine practice of axillary-lymph-node dissection in early breast cancer, the methods available for the histopathological assessment of lymph nodes, and the current thoughts about best surgical practice in the management of breast cancer. Sentinel-lymph-node biopsy has spread so rapidly that surgeons, pathologists, and patients are no longer willing or able to ignore the possible consequences of its implementation. A vast amount of data (over 1150 publications in the peer-reviewed literature on this subject to date) attests to the explosive interest in the past 5 years. In this article we review our own experience and discuss recommendations for clinical practice.

The correct identification of sentinel lymph nodes (SLNs) is paramount if this technique is to become the standard of care in the management of early disease in surgical oncology. Despite the apparent attraction and ease of this approach, a detailed understanding of its different technical components is vital. High sensitivity, reproducibility, and accuracy levels must be achieved in the identification and discrimination of the SLN if the extent and place of the standard lymph node diagnostic dissections can be challenged. This article reviews the technology and methodology and gives indications of the possible progress to be achieved.

Ventriculo-peritoneal (V-P) shunt is a frequently performed surgical procedure for treating hydrocephalus. The incidence of breast carcinoma in the UK is 20,000 cases per year. We present a case of a patient with breast carcinoma in association with V-P shunt.

Management of the axilla in breast cancer patients has been a subject of intense debate and controversy. Axillary lymph node status is still considered to be the single most important prognostic indicator in breast cancer patients. Despite a tendency toward a conservative approach for the surgery of primary breast carcinoma, axillary lymph node dissection (ALND) has remained an integral part of breast cancer management for more than a century. Among patients with T1/T2 tumors, up to 70% have a negative axillary dissection, and more than 50% of these node-negative patients develop morbidity related to ALND. It is ironic that the extent, morbidity, and cost of a staging procedure (ALND) is more than that of the surgical treatment of the primary tumor. We must readdress the question of axillary management in breast carcinoma in the light of information gained from the sentinel node biopsy trials around the world. We review the historical milestones and various modalities used for axillary management, discuss the concept of sentinel node biopsy for breast carcinoma, and propose a management plan.