Sentinel Lymph Node Analysis Research Articles

219. Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?

219. Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?

Intraoperative Sentinel Lymph Node Evaluation: Implications of Cytokeratin 19 Expression for the Adoption of OSNA in Oral Squamous Cell Carcinoma.

BackgroundIntraoperative analysis of sentinel lymph nodes would enhance the care of early-stage oral squamous cell carcinoma (OSCC). We determined the frequency and extent of cytokeratin 19 (CK19) expression in OSCC primary tumours and surrounding tissues to explore the feasibility of a “clinic-ready” intraoperative diagnostic test (one step nucleic acid amplification—OSNA, sysmex).MethodsTwo cohorts were assembled: cohort 1, OSCC with stage and site that closely match cases suitable for sentinel lymph node biopsy (SLNB); cohort 2, HNSCC with sufficient fresh tumour tissue available for the OSNA assay (>50 mg). CK19 assays included qRT-PCR, RNA in situ hybridisation (ISH), and immunohistochemistry (IHC), as well as OSNA.ResultsCK19 mRNA expression was detected with variable sensitivity, depending on method, in 60–80% of primary OSCC tumours, while protein expression was observed in only 50% of tumours. Discordance between different techniques indicated that OSNA was more sensitive than qRT-PCR or RNA-ISH, which in turn were more sensitive than IHC. OSNA results showed CK19 expression in 80% of primary cases, so if used for diagnosis of lymph node metastasis would lead to a false-negative result in 20% of patients with cervical lymph node metastases.ConclusionsOSNA in its current form is not suitable for use in OSCC SLNB due to inadequate expression of the CK19 target in all case. However, the same assay technology would likely be very promising if applied using a more ubiquitous squamous epithelial target.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-016-5337-6) contains supplementary material, which is available to authorized users.

“Intraoperative Touch Imprint Cytology of Sentinel Nodes”, Can it Serve as an Alternative to Frozen Section? – A Prospective Comparative Study of Touch Imprint Cytology and Frozen Section in the Intra Operative Assessment of Nodal Metastasis in Carcinoma Breast.

Sentinel lymph node biopsy (SLNB) is now known to offer an excellent alternative method to routine axillary lymph node dissection in staging of breast cancer. However, this minimally invasive technique requires facilities for frozen section (FS) and intraoperative analysis, which are sadly not available at most centers in India. At the same time Touch imprint cytology (TIC), is relatively less cumbersome technique for intraoperative assessment which may provide a fast and accurate method for intraoperative assessment of sentinel lymph nodes. Aim: This study was done to assess the accuracy and feasibility of using the TIC as an alternative to FS to assess metastasis in the sentinel node. Methods: Touch imprint cytological analysis of sentinel lymph nodes was compared prospectively with frozen section and the findings obtained on routine paraffin sections. Touch imprint slides from 32 consecutive women undergoing mastectomies (from Jan 2014 to May 2016) for invasive breast cancer (all 32 were T1-T3 and with clinically N0 nodal status) were prepared during operation from multiple sections of sentinel lymph nodes, stained with haematoxylin and eosin. Results: The sensitivity of TIC was 89.47% (95% CI, 68.49-98.81%), when compared with the final histopathological result as a gold standard method. The sensitivity of the FS was 94.74% (95% CI 73.97% to 99.87%), when compared to the HPE results. The specificity of the TIC and FS when compared to HPE is 100%. Conclusion: This study has lent credibility to the possible use of TIC as an assessment tool of the sentinel node in centers where facilities for frozen section are not available and hence expanding the population of potential beneficiaries who can be spared of morbidity associated with axillary dissection

The staging value of sentinel lymph node biopsy for breast cancer: translating pathologic findings to clinical practice.

Axillary nodal status is an important prognostic factor in guiding locoregional and systemic treatment for breast cancer. Sentinel lymph node biopsy (SNB) has revolutionized axillary staging by replacing axillary lymph node dissection (ALND) in node-negative women. Even in select patients whose sentinel lymph nodes (SLNs) contain metastases, SNB alone has become an accepted method of managing the axilla. Identification of micrometastases through immunohistochemical analysis of SLNs that are tumorfree on hematoxylin and eosin staining (H&E) does not confer additional clinical benefit. The use of SNB after neoadjuvant chemotherapy (NAC) remains controversial. In addition to axillary nodal status, tumor biology plays an increasingly important role in guiding therapeutic decisions.

Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?

e12037Background: The aim was to evaluate accuracy of intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLN) mapped using methylene blue dye (MBD) and its usefulness for selecti...

Abstract P1-06-08: Stem cell markers CD44+CD24- and ALDH1 in primary breast cancers and metastatic sentinel and non-sentinel lymph nodes

Abstract Background and Aim Studies of Aldehyde dehydrogenase 1 (ALDH-1) and CD44+/24- have suggested them as cancer stem cell (CSC) markers in breast cancers and the clinicopathologic and prognostic significance of these CSC markers have been widely investigated. However, expressions of CSC in metastatic axillary lymph nodes (ALN) of breast cancers have not yet been the center of interest. Therefore, the object of this study is to explore breast CSC markers CD44+CD24- and ALDH-1 in the primary breast tumor and metastatic ALNs by retrospectively analyzing the CSC expressions on metastatic tumor cells within ALN. Method 180 surgically resected breast cancers were selected and among them 165 cases had undergone sentinel lymph node (SLN) with or without non-sentinel lymph node (NSLN) dissections. 50 SLNs (30.3%) and 43 NSLNs (30.9%) had metastatic tumor cells and total of 74 cases were involved with axillary lymph node metastasis. Double immunohistochemistry of CD44/CD24 and single immunohistochemical staining of ALDH-1 were applied on paraffin embedded breast tissue specimens and lymph node specimens to evaluate the CSC phenotypes of primary tumor and metastatic lymph nodes. Results The prevalence of CD44+/CD24- and ALDH-1(+) tumor cells in primary breast cancer was 76.7% and 45.0%. In triple negative breast cancers (TNBC) contained significantly higher percentage (49.2%) of ALDH-1 positive tumor cells (p=0.001). CD44+/CD24- phenotype was present in 65.2% and 40.0% in metastatic SLNs and NSLNs, respectively. The analysis of metastatic sentinel lymph nodes and breast cancers with CSCs indicated that there are significant relationships with ALDH-1(+) (p<0.001) and CD44+/CD24- (p<0.001) phenotypes. CSC expression in metastatic NSLNs and breast tumors also showed significant association (p=0.001). However, CSCs in metastatic SLNs and NSLNs did not show any significant relationships to the intrinsic molecular subtypes. Conclusions This study investigated the impact of the stem/progenitor phenotype defined by CD44 positivity/CD24 negativity and ALDH-1 positivity in sentinel lymph nodes (SLN) on non-sentinel lymph node (NSLN) metastases. CSC phenotypes expressed in metastatic SLNs and NSLNs, independently showed significant association with the primary breast tumors. However, in future, the authors recommend that the exploration of a much larger study including a vast amount of pool will provide a more reliable result. Citation Format: Kim W, Kim Y-M, Kim W, Lee J-S. Stem cell markers CD44+CD24- and ALDH1 in primary breast cancers and metastatic sentinel and non-sentinel lymph nodes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-06-08.

Molecular Staging of Sentinel Lymph Nodes Identifies Melanoma Patients at Increased Risk of Nodal Recurrence

Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND). In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison. A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p= 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p=0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p= 0.9044). Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.

Intraoperative Histopathologic Assessment of Sentinel Lymph Nodes in Breast Cancer: An Evaluation of Institutional Protocol

Frozen section (FS) for evaluation of sentinel lymph nodes (SLNs) can be used to detect metastasis. However, there is no standard protocol concerning histopathologic analysis of SLNs on FS. Diverse methods have been proposed. Nonetheless, several issues such as cost, potential loss of micrometastasis, and sampling error, among other factors arose. This study highlights our institutional protocol in evaluating …

P115. The cytokeratin-19 mRNA copy number from one step nucleic acid amplification (OSNA) analysis of sentinel lymph nodes can be used in multiple ways to predict further axillary lymph node metastasis in patients with invasive breast cancer

P115. The cytokeratin-19 mRNA copy number from one step nucleic acid amplification (OSNA) analysis of sentinel lymph nodes can be used in multiple ways to predict further axillary lymph node metastasis in patients with invasive breast cancer

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

Ganglion sentinelle et mélanome

Cutaneous melanoma incidence has been increasing last 3 decades. Despite recent improvements in treatments, metastatic disease prognosis remains unfavorable. Lymph node involvement is a major prognosis factor in melanoma, and sentinel lymph node (SLN) biopsy becomes an essential procedure for nodal staging. SLN biopsy is available in most surgical cancer departments but procedure needs very strict achievement guidelines to allow a high level of performance. SLN biopsy could detect a prospective lymph node involvement with very high accuracy, along with very low morbidity. So, lymph node dissection would be performed only in a limited number of patients, increasing their disease free survival. However, in case of positive SLN, lymph node dissection interest as therapeutic act is still under debate and, in the future, indications of lymph node dissections will be purposed more accurately according to prognosis factors, especially histologic SLN analysis. Up to now, adjuvant treatments in melanoma were disappointing but new promising molecules are under research. According to researches results, SLN biopsy will probably allow a better selection of patients who should get benefit of those treatments.

Assessment of Sentinel Node Biopsies With Full-Field Optical Coherence Tomography.

Current techniques for the intraoperative analysis of sentinel lymph nodes during breast cancer surgery present drawbacks such as time and tissue consumption. Full-field optical coherence tomography is a novel noninvasive, high-resolution, fast imaging technique. This study investigated the use of full-field optical coherence tomography as an alternative technique for the intraoperative analysis of sentinel lymph nodes. Seventy-one axillary lymph nodes from 38 patients at Tenon Hospital were imaged minutes after excision with full-field optical coherence tomography in the pathology laboratory, before being handled for histological analysis. A pathologist performed a blind diagnosis (benign/malignant), based on the full-field optical coherence tomography images alone, which resulted in a sensitivity of 92% and a specificity of 83% (n = 65 samples). Regular feedback was given during the blind diagnosis, with thorough analysis of the images, such that features of normal and suspect nodes were identified in the images and compared with histology. A nonmedically trained imaging expert also performed a blind diagnosis aided by the reading criteria defined by the pathologist, which resulted in 85% sensitivity and 90% specificity (n = 71 samples). The number of false positives of the pathologist was reduced by 3 in a second blind reading a few months later. These results indicate that following adequate training, full-field optical coherence tomography can be an effective noninvasive diagnostic tool for extemporaneous sentinel node biopsy qualification.

The accuracy of intraoperative frozen section analysis of sentinel lymph nodes in patients with breast cancer

Background: The biopsy of sentinel lymph nodes (SLNs) has widely replaced conventional axillary lymph node dissection (ALND) for assessing the axillary lymph node (LN) status. Rapid intraoperative frozen section (FS) analysis of SLNs enables surgeon to perform ALND during the same operative procedure. However, there is an ongoing controversy regarding the accuracy and usefulness of FS for the evaluation of SLNs. The aim of the study was to investigate the accuracy of FS analysis in the management of patients with breast cancer. Patients and Methods: Between 2007 and 2014, 214 breast cancer patients who underwent SLN biopsy procedure with intraoperative FS were included in this retrospective study. The SLNs were examined using standard FS procedures, and each section was stained with hematoxylin and eosin (H and E) only. The remaining tissues were then further sectioned and examined with H and E postoperatively. The results of FS and permanent sections were compared (the sensitivity, specificity and accuracy of FS were calculated). Results: FS analysis detected LN metastases in 50 patients, while the permanent histopathologic examination detected metastases in another 9 patients. The sensitivity of FS for all kinds of metastases was 84.7%, but it reached up to 98% for macrometastases, and the specificity was 100%. FS allowed immediate completion of ALND in 50 patients (96%) with positive SLNs, and second-step surgery was only performed in 2 patients with discordant FS results. Conclusion: FS examination of SLNs is a reliable and safe procedure for the diagnosis of LN metastasis. FS provides immediate completion of ALND in case of metastatic disease in the SLNs.

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

L’étude peropératoire du ganglion sentinelle est devenue possible grâce à l’analyse moléculaire : nouveau concept et nouvelles applications pour les cancers coliques ?

Sentinel lymph node (SLN) is a concept but also a technical possibility that can be studied and applied to almost all organs with cancer. For colorectal cancer surgery, some possibilities of using the SLN are possible, other implausible and some completely new especially aware of possible analysis of SLN by a molecular biology technique. The orientation of dissection or “lymph road mapping” can be designed for this case or the surgeon may want to limit his actions, particularly in patients with a history of colonic surgical resection, to keep the digestive function in maintaining vascular axes considered not involved in the metastatic process. The use of the single analysis of SLN to determine the positive or negative status of the cleaning has failed because of the frequency of false negatives in part to the size of colic advanced cancers at diagnosis. The use of “ultra-stading” by multiple section or exhaustion of the block, can lead to reconsider a stage N0 to N1 as a point, if the analysis technique remains in HES. Unlike the “ultra-stading” by RT- PCR or immunohistochemistry was even more discussed and seems not equivalent in terms of prognosis and therefore no giving formally justification for adjuvant therapy. Currently, a new technique for molecular biology, named “OSNA”, allows an analysis of all the SLN in less than 45minutes. It is therefore possible to obtain during surgery analysis of a node with the same level of information than traditional analysis using HES. If this node is positive and if the strategy in case of positive lymph nodes was determined prior for this patient, it is possible to anticipate this strategy and place after colectomy during the same anesthesia, venous access quickly to start postoperative chemotherapy. This new technique for analyzing lymph applied to the SLN opens a new potential application of this concept in digestive oncology.

The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making

One Step Nucleic Acid Amplification (OSNA) method for the intraoperative analysis of sentinel lymph nodes (SLNs) in breast cancer, obviates a second operation to the axilla and thereby expedites progression to adjuvant therapy. Recent NICE guidelines have approved OSNA as a method of sentinel node diagnosis to support the above case.(1) METHOD: This is a single centre prospective cohort analysis of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to June 2012. Patients with negative SLN(s) on OSNA had no further axillary surgery. A validation phase was performed prior to using OSNA routinely. Those with micrometastases underwent a level 1 clearance, and >one SLN with macrometastases, underwent treatment by level 2 axillary dissection. The length of time from sentinel node retrieval to OSNA result was recorded. Four hundred and forty nodes were analysed in 212 patients with a mean age of 55 years (range 24-98). The sensitivity and specificity of OSNA was 93% and 94% respectively in cases of macrometastases. The process required additional median anaesthesia time of 20 min (range -48 to +65 min). Non-sentinel node positivity was 5% and 48% for micrometastasis and macrometastasis respectively. OSNA identified 62 of 212 patients with at least one positive sentinel node, thereby sparing 29% from a second procedure to clear the axilla subsequently. The median waiting time of 20 min for node results from completion of breast procedure is acceptable and allows for an efficient operating list. OSNA can be incorporated into routine practice and with improved methods of imaging preoperatively, can be an excellent adjunct to the breast cancer patient pathway of care.

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.