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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.

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.

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.

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.

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.

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 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.