Intraoperative Sentinel Lymph Node Analysis Research Articles

Intraoperative sentinel lymph node analysis after neoadjuvant chemotherapy in breast cancer patient - A 5 year single centre cohort study

Introduction: Intraoperative analysis (IOA) of sentinel lymph nodes is effective, and reliable for assessing node in breast cancer allowing for immediate clearance. Metasin® is a quantitative PCR Assay that detects CK 19 and mammaglobin. ABS guidance does not advocate IOA methods after neo-adjuvant chemotherapy (NACT) due to concern regarding detection of residual disease. We completed a retrospective comparative review of all consecutive patients who had IOA during SNB following NACT.

Does the result of the sentinel lymph node in breast cancer differ depending on the method of the intra-operative assessment used?

Background: Sentinel lymph node biopsy (SLNB) has been considered the preferred diagnostic procedure for sentinel lymph node (SLN) staging. There are two main techniques for intra-operative SLN analysis based on intraoperative histological (H&E) or molecular (OSNA) examination.The aim of our work is to understand the differences in the outcomes according to the use of one method versus the other.

Immediate intraoperative sentinel lymph node analysis by frozen section is predictive of lymph node metastasis in endometrial cancer.

Sentinel lymph nodes sampling (SLN) in endometrial cancer is being evaluated as a means to gather prognostic information about lymphatic metastasis while avoiding the morbidity associated with complete lymphadenectomy. SLN ultrastaging has been advocated to identify low-volume metastases, but its value remains uncertain. This study aims to evaluate a pathological protocol for the immediate intraoperative SLN work-up using H&E staining alone. In this retrospective single-center study, patients received standardized cervical injection of indocyanine green, SLN mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. SLNs were entirely frozen, multiple H&E stained sections prepared and evaluated intraoperatively. No immunohistochemistry was performed. SLN results were compared with the complete lymphadenectomy specimen. Over 3.5 years, 90 patients were identified who underwent SLN mapping and subsequent complete pelvic lymphadenectomy. At least one SLN was detected in 79 (88%) patients. The median number of SLNs removed was 2.0. Para-aortic SLNs were detected in 7%. Final pathology showed 67% Type I tumors, 76% locally confined. The mean number of lymph nodes removed during complete lymphadenectomy was 21. In this series, only 6 patients had lymph node metastases. 5/6 were identified by the described SLN approach resulting in 83.3% sensitivity and a negative predictive value of 98.7%. Our approach permits immediate intraoperative results and helps guide the primary surgery. The immediate SLN work-up using frozen sections showed both high accuracy and negative predictive value. The comparably lower sensitivity may be related to the low number of patients with positive lymph nodes (7.6%).

Abstract P3-01-14: Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes

Abstract Background: According to the American College of Surgeons Oncology Group Z0011 trial, complete axillary lymph node dissection (ALND) did not affect survival of patients with clinical T1-T2 invasive breast cancer and one to two sentinel lymph nodes (SLNs) metastases treated with lumpectomy, adjuvant systemic therapy, and radiation therapy. A significant proportion of breast cancer patients may not require ALND, in whom intraoperative analysis of SLNs can be omitted reducing operation time and cost. The aim of this study was to develop a nomogram predicting three or more axillary lymph nodes (ALNs) metastases based on preoperative imaging and clinicopathological factors. Methods: The training set consisted of 1030 patients with clinical T1-T2 invasive breast cancer and clinically negative ALN who received surgery at Seoul National University Hospital (SNUH) between January 2010 and December 2013. Preoperative imaging techniques including ultrasonography (US), computed tomography (CT), positron emission tomography (PET), and clinicopathological features associated with three or more ALN metastases were evaluated by logistic regression analysis. A nomogram predicting three or more ALNs was developed with statistically significant factors. The validation set consisted of 781 independent patients who received surgery at SNUH between January 2014 and December 2015. Results: Of the 1030 patients, 89 (8.6%) had three or more ALN metastases. Multivariate analysis showed that three or more ALN metastases was independently associated with tumor size (cm) by US (p<0.001), suspicious ALNs findings in US (p<0.001), chest CT (p<0.001), and PET/CT (≥ 1.4 SUV, p<0.001). Established nomogram evaluating the probability of three or more ALNs metastases includes the above four associated factors. The areas under the receiver operating characteristic (ROC) curve of the nomogram were 0.866 (95% confidence interval [CI] 0.826-0.905) for the training set and 0.867 (95% CI: 0.801-0.932) for the validation set. With cutoff point of 142, false negative ratio is 3.6%, and 8.6% of patients were candidates for intraoperative SLN analysis. Conclusion: Patients with a strong possibility of three or more ALNs metastases can be identified using preoperative imaging methods including US, CT, and PET. The nomogram measuring this prospect may be valuable in skipping intraoperative analysis of SLNs with advantage of reduced operation time and cost. Citation Format: Park JH, Ju YW, Kim KE, Rhu J, Kim Y, Lee E, Lee H-B, Moon H-G, Noh D-Y, Han W. Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-14.

Prediction of further axillary nodes metastatic load in breast cancer using the Metasin RTqPCR assay for CK19 and Mammaglobin during the intraoperative sentinel node analysis

Prediction of further axillary nodes metastatic load in breast cancer using the Metasin RTqPCR assay for CK19 and Mammaglobin during the intraoperative sentinel node analysis

Abstract P2-01-22: The long term outcomes of Metasin RTqPCR intra-operative sentinel node analysis in early breast cancer

Abstract Background: Axillary lymph node involvement is a prognostic factor in breast cancer and it is used to guide adjuvant therapy. Axillary clearance remains the standard of care in lymph node positive disease in most parts of the world. Usually this is performed as second procedure but immediate intra-operative node analysis allows clearance to be performed as part of the initial procedure where necessary. The Metasin assay targets the breast epithelial cell markers CK19 and mammaglobin mRNA and detects the presence of breast tissue (metastatic disease) in the sentinel nodes. Evidence shows the Metasin assay to be fast (average assay time 41.2min) and accurate with a discordance rate below 4% compared with histology. The cost effectiveness of the assay has been reported in our previous studies. Aim: The aim of this study is to assess the risk of axillary recurrence following the use of the Metasin assay to guide axillary management. Method: This is a single centre retrospective study which included all patients presenting to a district general hospital with early clinically node negative breast cancer undergoing sentinel node biopsy between Oct 2011 and Dec 2014. Alternate 2 mm slices of the node were examined intraoperatively using the Metasin assay and the remainder sent for histological examination. The results of the Metasin assay and histology were compared. The risk of axillary recurrence using the Metasin test to select patients for immediate axillary clearance was assessed. Results: 1073 sentinel nodes from 545 patients were analysed during this three-year period. 2 patients were lost to follow up. 94 patients were node positive and underwent axillary clearance as part of their primary surgery. 449 patients had sentinel node biopsy with no further axillary procedure. There were 36 nodes (3.34%) with discordant results. Median follow up was 32 months (range 18 to 55 months). Fourteen patients presented with recurrences (2.56%). The mean event free interval was 15 months. Of the 14 patients, 5 patients tested with Metasin had macrometastases and underwent immediate axillary clearance during the primary surgery. 7 patients were node negative and 2 patients were shown to have micrometastases. 11 patients recurred with distant metastases, 3 patients with local recurrence and 2 patients (0.36%) with axillary recurrences. The two axillary recurrences occurred at 3 and 5 months after primary surgery. Both patients underwent Metasin intraoperative analyses of sentinel nodes which were negative. Subsequent histological examination confirmed no metastatic node involvement in one patient but micro-metastases in the other. Both of these patients had aggressive disease with local, axillary and distant metastasis and subsequently died of their disease. Conclusions: The Metasin assay is a reliable intraoperative test for sentinel node involvement and when used to guide surgical axillary management is associated with very low axillary recurrences (0.36% with a median follow up of 32 months). Citation Format: Udayasankar S, Ashley E, Jenkins KS, Huws A, Sharaiha Y, Sai-Giridhar P, Thomas D, Munir A, Holt S, Khawaja S. The long term outcomes of Metasin RTqPCR intra-operative sentinel node analysis in early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-22.

Measuring the impact of the American College of Surgeons Oncology Group Z0011 trial on breast cancer surgery in a community health system

BackgroundThe American College of Surgeons Oncology Group Z0011 trial has been lauded as practice changing. We sought to identify its impact on breast cancer surgery in the community hospital setting. MethodsA retrospective review was performed from 8 community hospitals identifying patients with invasive breast cancer meeting the Z0011 criteria. The primary outcome measures were the rate of completion axillary lymph node dissection (ALND) and performance of intraoperative sentinel lymph node (SLN) analysis over time. ResultsA total of 1,125 lumpectomies with SLN biopsies were performed with 180 subjects meeting inclusion criteria. Performance of ALND (P < .0001) and intraoperative SLN analysis (P < .0001) declined during each time period. Patients more likely to undergo ALND included those with extracapsular extension (odds ratio [OR] 12.8, 95% confidence interval [CI] 2.5 to 67.1) and those who underwent reoperative surgery (OR 10.8, 95% CI 2.6 to 44.4) or intraoperative SLN analysis (OR 5.1, 95% CI 1.2 to 21.9). ConclusionAmerican College of Surgeons Oncology Group Z0011 trial has been rapidly practice changing in the community hospital setting.

Patient experience of intra-operative sentinel lymph node analysis

Patient experience of intra-operative sentinel lymph node analysis

Abstract P1-01-11: The health economics of one step nucleic acid amplification for intraoperative sentinel lymph node analysis in breast cancer

Abstract AIM Despite the obvious advantages of intraoperative sentinel lymph node (SLN) analysis in the form of One Step Nucleic Acid Amplification (OSNA), this technique has not been widely adopted in the United Kingdom. The aim of this study was to investigate the health economic implication of the technique. METHODS Data were collected prospectively on all patients undergoing OSNA at a single institution between September 2011 and February 2013. Initially patients were selected using the Sloan Kettering Nomogram for additional non SLN axillary disease [http://nomograms.mskcc.org] and patients with micrometastases were offered an axillary clearance. From August 2012, all patients undergoing sentinel node biopsy were offered OSNA. A cost analysis was done on the basis of up front purchase costs, OSNA cost per patient minus the cost of standard Haematoxylin and Eosin stain analyses at our institution and HRG4 codes. RESULTS Data were collected on 258 patients with a median age of 69. 209 (81%) had invasive ductal carcinoma. 208(80%) were oestrogen receptor positive and approximately 30% had lymphovascular invasion. Table 2 demonstrates the OSNA results. Table 1 - OSNA results Pre August 2012Post August 2012Total n%n%n%No. of patients169 88 257 Mean no. of nodes2.38 1.98 2.24 OSNA Negative11668.645461.3617066.15OSNA Micrometastases2715.982123.864818.68OSNA Macrometastases2112.431314.773413.23OSNA Inhibited52.960051.95Total no. undergoing Axillary Clearance5130.181820.456926.85Axillary Clearance for Micrometastases2313.6144.552710.51Additional nodes positive overall: 03772.55950.004666.671-3 nodes1121.57738.891826.094-7 nodes11.96211.1134.358-12 nodes11.96 11.45gt]12 nodes[11.96 11.45Additional nodes positive for OSNA Micrometastases: 021 22385.191-3 nodes2 414.81 The capital investment for setting up OSNA in our institution was £40,000. By carrying out OSNA on all patients undergoing sentinel node biopsy we saved a second procedure on 20% of patients. Table 2 outlines the costs saving per year based on the HRG4 code for the cost of second admission and axillary clearance. Table 2 - Health Economic Analysis TotalNo. patients undergoing OSNA per year235 Cost of OSNA per patient£286£67,210Cost of H &amp; E analysis based on 2 nodes per patient£101,60£23,876Net costs of OSNA per patient£184,40£43,334No. patients undergoing axillary clearance (20% of 235)47 Cost of axillary clearance (based on HRG4 JA07)£2,030£95,410Total saving per year with OSNA £52,076 CONCLUSION The use of OSNA as an intraoperative assessment of sentinel lymph nodes in breast cancer is a highly sensitive and efficient way of determining the sentinel node status. It saves patients undergoing a second admission and procedure. By offering OSNA to all patients undergoing SLN, the capital investment will be recouped in less than a year and the local health economy will save over £50,000 per year in subsequent years. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-11.

An evaluation of a tool to predict the probability of sentinel lymph node metastasis and its utilization in operative management

Introduction: Intraoperative analysis of Sentinel lymph-nodes (SLN) allows, if indicated, axillary clearance to be done during primary surgery thus avoiding a second procedure. Recent advances in preoperative axillary node staging have reduced the percentage of positive sentinel node biopsies with significant impact on theatre utilization. We evaluated a tool to identify a group of patients in whom routine intra-operative analysis of SLN can be avoided.

Repeat surgery following breast conservation and intra-operative sentinel lymph node analysis for breast cancer

IntroductionIntra-operative sentinel node analysis (IOA) for breast cancer reduces the need for a second operation by revealing metastasis intra-operatively, allowing immediate axillary clearance. Critics argue that the number of patients deriving benefit is limited, as further surgery is often required for reasons other than nodal status. AimTo identify the proportion of women avoiding further surgery by using IOA excluding those who require further surgery for reasons other than axillary node metastasis. Patients and methodsAll patients undergoing sentinel node biopsy with IOA over one year were reviewed. Patient demographics, margin positivity, sentinel node metastasis, requirement for further surgery, and cavity shave involvement were analysed. Results322 patients were analysed: 253 undergoing breast-conserving surgery [BCS] and 69 undergoing mastectomy). IOA revealed metastasis in 81 (25.2.%) patients [25 undergoing mastectomy and 56 undergoing BCS], who underwent immediate axillary clearance. 43 BCS patients (17%) did not require further surgery other than for sentinel node involvement. 39 patients required further oncological surgery: 16 excision of margins; 13 completion mastectomy; 6 excision of margins followed by mastectomy; 3 completion axillary clearance; and 1 excision of recurrence. 20.6% had involvement of any circumferential histological margin. Cavity shaves were performed in 28.5% patients at initial surgery, the majority of which were clear of malignancy. 20 mastectomy patients had concordant definitive histology, avoiding a second operation. In total, 19.6% of this cohort avoided a second operation through the use of IOA. DiscussionApproximately 15% of patients undergoing breast conservation surgery for breast cancer require further surgery. However, a further 17% were saved subsequent surgery by utilising IOA, since they had immediate axillary clearance. When also considering patients undergoing mastectomy, this proportion is even higher.

Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer – a single laboratory audit

Background Intraoperative sentinel lymph node (SLN) assessment is currently under scrutiny for its utility in the immediate management of breast cancer patients. Aim To determine the utility of frozen section (FS) analysis of SLNs by calculating the sensitivity and specificity of metastatic deposit detection. Methods Breast cancer pathology reports including intraoperative SLN FS analysis were retrieved from our laboratory database from the period of July 2011 to the present. The final tumour diagnosis, tumour grade, number and size of SLNs analysed, frozen section findings, H&E and immunohistochemical findings, and size of tumour metastases within the sentinel node were recorded. Results To date, a total of 197 records including 310 sentinel lymph nodes have been retrieved. Of these nodes, 62 were identified as having metastatic tumour deposits. Thirty-eight lymph nodes containing metastatic deposits were identified at frozen section and 24 were initially reported as having no meta-static disease (sensitivity 61%, specificity 100%). No isolated tumour cell (ITC) deposits were identified on frozen section, and 35% and 84% of micro- and macrometastases were identified, respectively. Conclusions Intraoperative sentinel node analysis is a useful tool for detecting metastatic deposits. Larger metastatic deposits are more frequently identified in the first instance than mi-crometastasis or ITCs. Other tumour-related factors such as tumour type and grade may be considered in predicting SLN metastasis.

Abstract P1-01-18: The results of 55 consecutive cases of intra-operative sentinel node analysis using real time polymerase chain reaction detection of cytokeratin 19 and mammoglobin expression (Metasin) to direct immediate axillary clearance.

Abstract The standard management of early beast cancer is complete excision of the primary from the breast by either wide local excision or mastectomy and sentinel node biopsy to stage the axilla. The standard of care in the UK remains clearance of the axilla in node positive patients. Unless immediate multiple frozen section histology is available, positive patients require a second operation between 3 and 6 weeks later, with the associated increased cost, inconvenience and risk. By using the real time polymerase chain reaction (PCR) to detect mammary derived cells in the sentinel lymph nodes (SLN), we aim to provide the surgeon with a reliable indicator of the presence or absence of nodal macro-metastases within a timeframe that will allow axillary clearance to be performed under the same anaesthetic as the initial surgery. We detect cytokeratin 19 (CK19) or mammoglobin within the lymph node using reagents developed by the UK National Health Service under the name Metasin. Method: 55 consecutive patients undergoing SLN biopsy as part of their initial treatment for early breast cancer were tested using the Metasin. The nodes were divided into 2mm slices and alternate sections submitted to PCR and the remainder to conventional histology. The results were compared and an assessment of the costs made. The time taken report the Metasin result to the surgeon was recorded. Results: Five patients had positive results by Metasin and proceeded to immediate axillary clearance. When compared to histology there were no false positive results (0%). Two patients were negative on Metasin testing with the threshold set at 2 mm but positive on histology (3.6%). The average time for the test was 43.2 minutes and the mean number of lymph nodes was 2.3. The average cost is £40 to test 2 nodes. Discussion: The test is accurate. The two false negative cases were found to be due to the sampling, the metastases being only present by chance in the histologically examined specimens and not due to assay failure. The total cost to run the test for 55 patients was £2,520. The cost for completion axillary clearance as a separate procedure is estimated at £2,227. The total saving for 5 cases is about £11,000, making the test cost saving as well as safer, more acceptable to the patients and limiting delay in starting adjuvant therapies. The additional time of surgery caused by using Metasin was minimal. Conclusion: Metasin has become our standard of care in patients requiring SLN biopsy and generally avoids second surgeries to clear the axilla in positive cases. We are considering analyzing the complete node using this technique and this would eliminate false negatives caused by sampling and offer further cost savings in the histology department. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-18.

Repeat surgery following Breast Conservation and Intra-operative Sentinel Lymph Node Analysis for Breast Cancer

Abstract Introduction Intra-operative sentinel node analysis (IOA) for breast cancer reduces the need for a second operation by revealing metastasis intra-operatively, allowing immediate axillary clearance. Critics argue that the number of patients deriving benefit is limited, as further surgery is often required for reasons other than nodal status. Aim To identify the proportion of women avoiding further surgery by using IOA excluding those who require further surgery for reasons other than axillary node metastasis. Patients and methods All patients undergoing sentinel node biopsy with IOA over one year were reviewed. Patient demographics, margin positivity, sentinel node metastasis, requirement for further surgery, and cavity shave involvement were analysed. Results 322 patients were analysed: 253 undergoing breast-conserving surgery [BCS] and 69 undergoing mastectomy). IOA revealed metastasis in 81 (25.2.%) patients [25 undergoing mastectomy and 56 undergoing BCS], who underwent immediate axillary clearance. 43 BCS patients (17%) did not require further surgery other than for sentinel node involvement. 39 patients required further oncological surgery: 16 excision of margins; 13 completion mastectomy; 6 excision of margins followed by mastectomy; 3 completion axillary clearance; and 1 excision of recurrence. 20.6% had involvement of any circumferential histological margin. Cavity shaves were performed in 28.5% patients at initial surgery, the majority of which were clear of malignancy. 20 mastectomy patients had concordant definitive histology, avoiding a second operation. In total, 19.6% of this cohort avoided a second operation through the use of IOA. Discussion Approximately 15% of patients undergoing breast conservation surgery for breast cancer require further surgery. However, a further 17% were saved subsequent surgery by utilising IOA, since they had immediate axillary clearance. When also considering patients undergoing mastectomy, this proportion is even higher.

Do we need intraoperative sentinel lymph node analysis when preoperative ultrasound staging is so accurate?

Introduction: Preoperative axillary ultrasound is a mandatory staging investigation for patients with breast cancer. We analysed data to evaluate the accuracy of ultrasound in our unit and correlated this with postoperative histopathology. In particular we aimed to determine if those patients with lymph node metastasis, in whom a preoperative diagnosis was not made, have low volume metastatic disease. Following publication of the results of ACOSOG Z0011, axillary lymph node dissection may not be required for all patients with a positive sentinel lymph node, especially those with low volume disease.

P3-07-28: One Step Nucleic Acid Amplification (OSNA) for Intraoperative Molecular Detection of Lymph Node Metastases and Micro-Metastases in Breast Cancer.

Abstract Introduction: Ideally, intraoperative sentinel lymph node analysis in breast cancer should be automated, concordant with histopathology and practically applicable. One step nucleic acid amplification (OSNA), a highly sensitive intraoperative assay of cytokeratin 19 mRNA, is used for the detection of sentinel lymph node (SLN) macro- and micro-metastases in breast cancer. Guildford adopted the intraoperative OSNA “live” in December 2008 after undertaking a multicentre evaluation of its accuracy and high concordance with histopathology and here we present our two year data since its introduction. Methods: Data was collected prospectively from 2008–10. All patients eligible for sentinel node biopsy were offered OSNA and operations were performed by five consultant breast surgeons. On detection of micro-metastasis (+) and positive but inhibited metastases a level 1 axillary nodal clearance (ANC) and for a macro-metastasis (++), a level 3 ANC was performed. Results: 471 patients had 999 SLN analysed, median age being 61. All except one were females. 72% (n=340) had wide local excision, 26% (n=120) underwent mastectomy and 2% (8) SNB alone. Mean tumour size was 18.3 mms. 80% (n=371) of the cases were IDC and 55% (n=256) had grade II tumour. 34% (n=161/471) had positive SLN who had further ANC. Of these, 48% (n=78/161) had macro-metastases, 37% (n=59/161) had micro-metastases and 15% (n=24/161) had positive but inhibited results. 17% (10/59) of the patients with micrometastases had positive non-SLN (NSLN), four (4/59, 6.8%) had four positive nodes (SLN+NSLN) thus receiving adjuvant radiotherapy. 8% (2/24) of those with positive but inhibited results and 39% (30/78) of those with macro-metastases had positive NSLN. Conclusion: Over a third of patients had OSNA positive SLN and underwent axillary surgery at the same operation. This technique eliminates the need for a second operation in sentinel lymph node positive patients and avoids the anxious wait for results in all, streamlining the patient's cancer journey. OSNA upstages patients with micro-metastases and long term studies are needed to determine the clinical relevance of molecular micro-metastatic disease. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-28.

Intraoperative assessment of sentinel lymph nodes in breast cancer.

Sentinel lymph node biopsy (SLNB) reduces the morbidity of axillary clearance and is the standard of care for patients with clinically node-negative breast cancer. The ability to analyse the sentinel node during surgery enables a decision to be made whether to proceed to full axillary clearance during primary surgery, thus avoiding a second procedure in node-positive patients. Current evidence for intraoperative sentinel node analysis following SLNB in breast cancer was reviewed and evaluated, based on articles obtained from a MEDLINE search using the terms 'sentinel node', 'intra-operative' and 'breast cancer'. Current methods for evaluating the sentinel node during surgery include cytological and histological techniques. Newer quantitative molecular assays have been the subject of much recent clinical research. Pathological techniques of intraoperative SLNB analysis such as touch imprint cytology and frozen section have a high specificity, but a lower and more variably reported sensitivity. Molecular techniques are potentially able to sample a greater proportion of the sentinel node, and could have higher sensitivity.

Intraoperative Sentinel Node Analysis in Breast Cancer - A pilot study of OSNA and imprint cytology

Introduction: Sentinel node analysis is critical for staging patients with breast cancer and thus determining their treatment. At present most centres rely on departmental histological analysis of sentinel nodes using haematoxylin and eosin staining. This can take 3-4 days, requiring patients to have a second procedure for an axillary clearance. This is distressing for the patient, financially draining and congests operating lists. OSNA (One-step Nucleic Acid Amplification) has been advocated as one method for intra-operative lymph node analysis.

Intra-operative sentinel lymph node biopsy (SNB) using an RT-PCR based assay allows savings in theatre utilisation and hospital stay

Introduction: Theatre times are slightly increased with intra-operative sentinel node analysis (ioaSNB), however node positive patients avoid a second hospital admission and a second operation. It is uncertain if overall this leads to changes in theatre and hospital bed utilisation.

Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.