Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: Experience from a London Teaching Hospital

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.     

The use of one step nucleic-acid amplification (OSNA) in clinical practice: A single-centre study

BackgroundThe development of intraoperative sentinel node biopsy (SLNB) analysis methods, such as One-Step Nucleic Acid Amplification (OSNA), has made single-stage procedures possible.AimsWe investigated the incidence of OSNA-detected lymph node positivity, comparing it to conventional histopathology, the incidence of non-SLNB node disease for the OSNA positive patients, and the breast re-operation rate, to assess the benefit from single-stage procedures.MethodsThis was a single-centre series of 573 consecutive patients undergoing SLNB (173 histopathology and 400 OSNA).ResultsOSNA-detected SLNB macrometastasis was similar to routine histopathology, with more micrometastasis detected (p < 0.001). Non-SLNB involvement in the OSNA group was similar to documented histopathological series. 27.6% of OSNA patients avoided further surgery because of OSNA. The median time for OSNA results was 42 min.ConclusionsOSNA is an effective method for detecting SLNB-metastasis. It is easily used in clinical practice, providing reliable results and negating the need for a second axillary operation.     

Sentinel and nonsentinel lymph node assessment using a combination of one-step nucleic acid amplification and conventional histological examination

BackgroundClinical significance of intraoperative sentinel lymph node (SLN) metastases detection using one-step nucleic acid amplification (OSNA) has not been thoroughly investigated. The aim of this study was to assess the usefulness of using a combination of OSNA and conventional histological examinations.Materials and methodsWe included 772 consecutive patients with clinical node-negative cTis-cT3 primary breast cancer who underwent SLN biopsy with intraoperative OSNA and multi-section histological examination at our institution. We estimated the concordance rate and compared SLN metastases detection rates between the two methods. We also compared non-SLN metastasis detection rate between patients who tested positive in OSNA and those who tested positive in histology.ResultsAmong 772 patients, SLN metastases were intraoperatively detected in 211 (26.4%) by either OSNA or histology, in 168 (21.8%) by OSNA, and in 150 (19.4%) by histology. The concordance rate between OSNA and histological examination was 89.2%, but only 123 (58.8%) patients tested positive in both OSNA and histology; 45 were positive in OSNA only and 43 were positive in histology only.SLN status as per both OSNA and histology was significantly correlated with the presence of non-SLN metastases and multivariate analysis-identified independent predictive factors of non-SLN metastases.ConclusionsIntraoperative SLN metastases detection may be more accurate with a combination of OSNA and histological examination than with OSNA or histological examination alone. By using both methods, we can reduce the risk of false negative rate in SLN biopsy, and may prevent physicians from overlooking patients with non-SLN metastases.     

Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection

PurposeSentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). Intraoperative assessment of SLN by frozen sections can produce false negative results. The aim of this study was to compare two different techniques of intraoperative assessment of SLN in breast cancer patients treated with NAC: frozen section (FS) and molecular assay (OSNA).MethodsA multicenter cohort of 320 consecutive breast cancer patients treated with NAC between 2010 and 2014 was analyzed. FS was performed intraoperatively in 166 patients (H&E cohort) and OSNA in 154 patients (OSNA cohort).ResultsA mean of 2.15 SLNs by FS and 1.22 SLNs by OSNA was assessed (p = 0.03). SLN metastasis was found in 44 patients (26.5%) by FS and in 48 (31.2%) by OSNA (p = 0.4). There was no statistical significance in rates of macrometastasis (75%), micrometastasis (20.5%) or ITCs (4.5%) when assessed by FS compared to OSNA (52.3%, 36.3% and 11.4%, respectively) (p = 0.06). There were 10 patients in the H&E cohort with positive-SLN in the definitive pathology assessment with negative intraoperative FS. When OSNA and definitive pathology were compared, there were no differences in rates of macrometastasis (61.1%), micrometastasis (33.3%) nor ITCs (5.6%) (p = 0.5). Fifty-four patients in the H&E cohort and 44 in the OSNA cohort had ALND after positive-SLNs. ALND was performed in a second surgery in 10 patients (18.5%) in the H&E cohort for intraoperative FS false negative results, 90% being micrometastasis. 42 out of 44 patients (95.5%) in the OSNA cohort had an ALND in the same surgery (p = 0.03).ConclusionsOSNA assay detects SLNs metastases as accurately as conventional pathology in the NAC setting. Intraoperative definitive assessment of the SLN by OSNA reduces the need for a second surgery for ALND in 18.5% of breast cancer patients with a positive-SLN after NAC.     

One-Step Nucleic Acid Amplification (OSNA) for the Application of Sentinel Node Concept in Gastric Cancer

Purpose

This study was designed to apply safely the sentinel node navigation surgery (SNNS) to the malignancies, an accurate and prompt intraoperative diagnosis of SN is essential, and micrometastasis has been frequently missed by conventional frozen sections. Recently, a novel molecular-based rapid diagnosis for the lymph node (LN) metastases has been developed using (OSNA) in breast cancer, which takes approximately 30 min to obtain a final result. We evaluated the efficacy of OSNA in terms of the intraoperative diagnosis of LN metastasis in patients with gastric cancer.

Methods

A total of 162 LNs dissected from 32 patients with gastric cancer was included in this study; 45 LNs were pathologically diagnosed as metastatic LNs and 117 LNs were negative. The LNs were bisected; halves were examined with H&;E stain, and the opposite halves were subjected to OSNA analyses of CK19 mRNA. The CK19 mRNA expression was examined in the positive or negative metastatic LNs, and the correlation between the tumor volume and CK19 mRNA expression in the metastatic LNs was examined.

Results

The CK19 mRNA expressions in the positive metastatic LNs were significantly higher than those of negative LNs. When 250 copies/μl was set as a cutoff value, the concordance rate was 94.4%, the sensitivity was 88.9%, and the specificity was 96.6%. The OSNA expression was significantly correlated with the estimated tumor volumes in the metastatic LNs.

Conclusions

The OSNA method is feasible and acceptable for detecting LN metastases in patients with gastric cancer. This should be applied for the intraoperative diagnosis in the SN-navigation surgery in gastric cancer.

     

乳腺癌前哨淋巴结转移术中检测进展：一步法核酸扩增技术

乳腺癌已成为女性最常见的恶性肿瘤之一,腋窝淋巴结（ALN）转移是乳腺癌最主要的转移方式,其是判断预后和指导术后辅助治疗方案决策最重要的指标。腋窝淋巴结清扫（ALND）是评估ALN状态最准确的方法,亦是造成上肢淋巴水肿、疼痛、感觉障碍等并发症的主要原因。随着早期乳腺癌的增多,ALN阴性乳腺癌已占据一半以上,如对所有乳腺癌患者行ALND,将只有少部分患者受益,大部分患者接受了过度治疗。乳腺癌前哨淋巴结（SLN）是乳腺癌患者肿瘤细胞经淋巴结转移的首道屏障。历经数十年发展,前哨淋巴结活检（SLNB）已成为乳腺癌患者ALN状态分期的标准程序,常用于确定乳腺癌治疗方式的选择。准确、快速的SLN术中诊断可以使SLN阴性的乳腺癌患者避免ALND,SLN阳性患者通过一次手术完成ALND,避免二次手术的费用负担和手术风险。术中检测SLN是否转移常用的病理学方法是冷冻切片和印片细胞学检查,这两种常规病理检测方法仅检测SLN的代表性切片,均存在敏感度较低、主观性、非标准化、检测的组织量少（远远低于5%）、没有统一诊断标准等缺点,因此临床上迫切需要一种结果准确,操作简便的新型检测方法。近年来分子诊断技术迅速发展,一步法核酸扩增（OSNA）是通过逆转录环介导的靶向细胞角蛋白19mRNA等温扩增法精确检测术中乳腺癌淋巴结转移的分子诊断方法。OSNA检测运作时间约30~40 min,在SLN检测分析中,OSNA的准确率、敏感度均优于常规病理学检测方法。术中快速定量可区分宏转移和微转移,指导手术方案,并且在检测SLN微转移时,OSNA也更胜一筹。笔者对OSNA检测在乳腺癌SLN转移中的进展及应用前景做一综述。     

Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer

BackgroundThis study aimed to determine the relationship between CK19 mRNA copy number in sentinel lymph nodes (SLN) assessed by one-step nucleic acid amplification (OSNA) technique, and non-sentinel lymph nodes (NSLN) metastization in invasive breast cancer. A model using total tumor load (TTL) obtained by OSNA technique was also constructed to evaluate its predictability.MethodsWe conducted an observational retrospective study including 598 patients with clinically T1-T3 and node negative invasive breast cancer. Of the 88 patients with positive SLN, 58 patients fulfill the inclusion criteria.ResultsIn the analyzed group 25.86% had at least one positive NSLN in axillary lymph node dissection. Univariate analysis showed that tumor size, TTL and number of SLN macrometastases were predictive factors for NSLN metastases. In multivariate analysis just the TTL was predictive for positive NSLN (OR 2.67; 95% CI 1.06–6.70; P = 0.036). The ROC curve for the model using TTL alone was obtained and an AUC of 0.805 (95% CI 0.69–0.92) was achieved. For TTL >1.9 × 10⁵ copies/μL we got 73.3% sensitivity, 74.4% specificity and 88.9% negative predictive value to predict NSLN metastases.ConclusionWhen using OSNA technique to evaluate SLN, NSLN metastases can be predicted intraoperatively. This prediction tool could help in decision for axillary lymph node dissection.     

Intraoperative Nomograms,Based on One-Step Nucleic Acid Amplification,for Prediction of Non-sentinel Node Metastasis and Four or More Axillary Node Metastases in Breast Cancer Patients with Sentinel Node Metastasis

Background

One-step nucleic acid amplification (OSNA) for cytokeratin 19 messenger RNA is an intraoperative diagnostic procedure for the detection of lymph node metastasis.

Objective

This study aimed to construct intraoperative nomograms using OSNA for the prediction of non-sentinel lymph node (NSLN) metastasis and four or more axillary lymph node (ALN) metastases.

Methods

Of the 4736 breast cancer patients (T1-3, N0) who underwent sentinel lymph node (SLN) biopsy and had SLNs examined intraoperatively with OSNA, 623 with SLN metastasis treated with completion ALN dissection (cALND) were retrospectively analyzed, and were randomly divided into training (n?=?312) and validation (n?=?311) sets.

Results

Of the clinicopathological parameters available preoperatively and intraoperatively, the multivariate analysis of the training set revealed that clinical tumor size and total tumor load (TTL) determined by OSNA were significantly associated with NSLN metastasis, and that clinical tumor size, number of macrometastatic SLNs, and TTL were significantly associated with four or more ALN metastases. Nomograms for NSLN metastasis and four or more ALN metastases were constructed using these parameters, and their area under the receiver operating characteristic curve (AUC) of the validation set were both 0.70, with a diagnostic accuracy similar to that of previously reported postoperative nomograms.

Conclusions

We constructed intraoperative nomograms using OSNA for the prediction of NSLN metastasis and four or more ALN metastases. These nomograms are as accurate as the conventional postoperative nomograms and might be helpful for decision making regarding the indication for cALND or the choice of adjuvant chemotherapeutic regimens and radiation field.

     

Intraoperative Molecular Assessment for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma Using One-Step Nucleic Acid Amplification (OSNA) Assay

Background

Conventional intraoperative pathological examination for Sentinel node navigation surgery (SNNS) has been controversial. We evaluated the efficacy of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis of cervical lymph node (CLN) metastasis compared with histopathological examination in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 175 CLNs dissected from 56 patients with HNSCC who underwent surgery at Aichi Cancer Center, Kyorin University, Gunma University or Fukushima Medical University, between April 2008 and December 2011 were enrolled. CLN samples were sectioned into four equal pieces, with two of each used for OSNA assay and other histopathological examinations. The diagnostic value of OSNA assay in HNSCC patients in predicting the results of histopathological diagnosis was evaluated using the area under the receiver operating characteristic (AUROC) curve.

Results

OSNA assay showed acceptable efficacy in the detection of pathological CLN metastasis (AUROC 0.918, 95?% confidence interval [CI] 0.852?C0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC patients was 131?copies/??l (sensitivity: 82.4, 95?% CI 65.5?C93.2; specificity: 99.3, 95?% CI 96.1?C100.0; positive likelihood ratio 116.1; negative likelihood ratio 0.2].

Conclusions

We demonstrated that OSNA assay is useful in intraoperative diagnosis for CLN metastasis in patients with HNSCC. OSNA assay could be applied for SNNS in HNSCC patients.     

Is OSNA better than imprint cytology for intraoperative diagnosis of cancer involvement of axillary sentinel node in breast cancer?

ObjectiveThe study aim was to establish Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value (NPV), and Accuracy Values of both imprint cytology (IC) and the OSNA assay for intraoperative assessment of axillary sentinel node (SN) cancer involvement in breast cancer. Specifically, we wished to find out if true positive and false negative results of IC were associated to axillary lymphadenectomy (ALND). Also, we addressed a comparative cost analysis between techniques.Methods244 patients treated for breast cancer in the Breast Unit of Hospital Germans Trias i Pujol from 2011 to 2015 were prospectively included. A transversal, consecutive design was applied to assess IC compared to the reference test (OSNA). Inclusion criteria were: T1 and T2 tumors with negative nodes, both clinically and on ultrasound.ResultsSensitivity of IC for macrometastases was 70%. The NPV of IC for macrometastases was 95,75%. Accuracy of IC was 96,12%. In the comparative cost analysis, the release time of results for OSNA doubled that of IC and was associated with an increased cost of € 370.ConclusionsIC has been stated as a good technique for intraoperative cancer involvement SN with high sensitivity and NPV compared to the OSNA assay. It allows keeping the whole node tissue and thus the possibility of improved histopathological evaluation, which can be useful for adjuvant, and offers the advantage of being less time consuming. Cost analysis shows a higher cost for OSNA, which may exceed the benefit of sorting out false negatives from IC.     

Performance of four published risk models to predict sentinel lymph-node involvement in Australian women with early breast cancer

BackgroundSentinel lymph-node biopsy has reduced the need for extensive axillary surgery for staging. It still exposes women to associated morbidity. Risk models that use clinical and pathology information of the primary tumour to predict sentinel lymph-node metastasis may allow further improvements in care. This study assessed the performance of four published risk models for predicting sentinel lymph-node metastasis in Australian women with early breast cancer; including one model developed in an Australian population.MethodsThe Sentinel Node Biopsy Versus Axillary Clearance (SNAC) trial dataset was used to assess model discrimination by calculating the area under the receiver-operating-characteristic curve (AUC) and the false-negative rate for sentinel lymph-node metastasis using model-predicted risk cut-points of 10%, 20%, 30%, and calibration using Hosmer-Lemeshow tests and calibration plots.ResultsThe sentinel node was positive in 248 of 982 (25.2%) women (158 macrometastasis, 90 micrometastasis). The AUCs of risk models ranged from 0.70 to 0.74 for prediction of any sentinel-node metastasis; 0.72 to 0.75 for macrometastasis. Calibration was poor for the three models developed outside of Australia (lack-of-fit statistics, P < 0.001). For women with a model-predicted risk of sentinel lymph-node metastasis ≤10%, observed risk was 0–13% (three models <10%), false-negative rate 0–9%; 1–17% of women were classified in this range.ConclusionAll four models showed good discrimination for predicting sentinel lymph-node metastasis, in particular for macrometastasis. With further development such risk models could have a role in the provision of reassurance to low risk women with normal nodes sonographicaally for whom no axillary surgery is contemplated.     

Selective Extirpation of Tattooed Lymph Node in Combination with Sentinel Lymph Node Biopsy in the Management of Node-Positive Breast Cancer Patients after Neoadjuvant Systemic Therapy

IntroductionAxillary dissection has little diagnostic and therapeutic benefit in node-positive breast cancer patients in whom axillary disease has been completely eradicated after neoadjuvant chemotherapy (ypN0). We sought to assess the efficacy of an algorithm used for the identification of the ypN0 patient consisting of intraoperative evaluation of sentinel and tattooed (initially positive) lymph nodes.MethodsIncluded were T1 and T2 breast cancer patients with 1–3 positive axillary lymph nodes marked with carbon who were referred for neoadjuvant chemotherapy followed by a surgery. Axillary dissection was performed only in the patients with residual axillary disease after neoadjuvant chemotherapy on ultrasound or with metastases described in the sentinel or tattooed lymph nodes either intraoperatively or in the final histology.ResultsOut of 62 initially included node-positive patients, 15 (24%) were spared axillary dissection. The detection rate of tattooed lymph nodes after neoadjuvant chemotherapy was 81%. The ypN0 patients were identified with 91% sensitivity and 38% specificity using ultrasound and intraoperative assessment of both sentinel and tattooed lymph node according to the final histology.Discussion/ConclusionLymph node marking with carbon dye is a useful and cost-effective method, which can be successfully implemented in order to reduce the number of patients undergoing axillary dissection. Low specificity of the presented algorithm was caused mostly by the overestimation of residual axillary disease on ultrasound.     

Frozen Section Investigation of the Sentinel Node in Malignant Melanoma and Breast Cancer

Background: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients.Methods: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis.Results: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively.Conclusion: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.Presented, in part, at the 4th World Conference on Melanoma, Sydney, Australia, June 10–14, 1997, and the 10th Congress of the European Society of Surgical Oncology, Groningen, the Netherlands, April 5–8, 2010434_2001_Article_222.     

Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary.     

Feasibility and reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients with positive axillary nodes at initial diagnosis: An up-to-date meta-analysis of 3,578 patients

PurposeNeoadjuvant chemotherapy (NACT) is increasingly adopted in the therapy of breast cancer (BC) patients with positive axillary nodes (cN+), but the reliability and feasibility of sentinel lymph node biopsy (SLNB) following NACT are still controversial. The objective of the present study is to conduct an updated meta-analysis on this issue.MethodsA literature search was performed using PubMed, Cochrane, Embase, and Web of Science to identify papers published from January 1, 2000 to October 22, 2020 to research SLNB after NACT in BC patients. Studies that met the quality standard were enrolled for this meta-analysis.ResultsA total of 3578 participants from 27 trials were included in this meta-analysis. The pooled estimate of the identification rate (IR) for SLNB was 91 %, and the false negative rate (FNR) was 15 %. The pooled negative prediction value (NPV), accuracy, specificity, and sensitivity were 82 %, 89 %, 97 %, and 85 %, respectively. In subgroup analysis, the application of dual mapping could clearly decrease the FNR. The FNR was significantly high in the luminal types, and it declined as more sentinel lymph nodes (SLNs) were removed.ConclusionSLNB following NACT is now technically feasible for BC with cN+. However, it must be emphasized that the FNR is unacceptable high.     

One-step nucleic acid amplification assay for intraoperative prediction of non-sentinel lymph node metastasis in breast cancer patients with sentinel lymph node metastasis

The aim of the present study was to construct the intra-operative prediction model of non-sentinel lymph node (non-SLN) metastasis in breast cancer patients with SLN metastasis using one-step nucleic acid amplification (OSNA). Of 833 breast cancer patients (T1-T2, N0) who underwent SLN biopsy and had their SLNs examined intra-operatively with the OSNA assay, 161 with SLN metastasis and treated with completion axillary lymph node dissection (cALND) were randomly divided into a training (n = 81) and a validation (n = 80) cohort. Non-SLN metastasis of the training cohort was associated with the number of positive SLNs (P = 0.001), CK19 mRNA copy number (P = 0.001), and clinical tumor size (P = 0.055). These parameters were used to construct the intra-operative prediction model of non-SLN metastasis. Its diagnostic accuracy (AUC of ROC curve) was 0.809 and 0.704 for the training and validation cohorts, respectively. The intra-operative prediction model using OSNA may have a diagnostic accuracy of non-SLN metastasis comparable to that of the conventional, post-operative prediction model, indicating that it might help decide the indication for cALND.     

Tumoral load quantification of positive sentinel lymph nodes in breast cancer to predict more than two involved nodes

AimOne-Step Nucleic Acid Amplification (OSNA) can detect isolated tumour loads in axillary lymph nodes of breast cancer patients. We investigated the predictability of the non-sentinel lymph node (SLN) metastatic involvement (MI) based on the OSNA SLN assessment in surgical invasive breast cancer.MethodsWe studied surgical breast invasive carcinoma patients, not taking neoadjuvant chemotherapy, having SLN positive by OSNA and having received axillary lymphadenectomy. Age, basic histopathological, immunohistochemical, SLN biopsy and lymphadenectomy data were compared between patients with or without MI of more than 2 non-SLN in both univariate and multivariate analyses. The discriminating capacity of the multivariate model was characterized by the ROC AUC.Results726 patients from 23 centers in Spain aged 55.3 ± 12.2 years were analysed. The univariate analysis comparing patients with or without MI of more than 2 non-SLN detected statistically significant differences in primary tumour size, multifocality, presence of lymphovascular infiltration, positive proliferation index with ki67, immunophenotype and logTTL (Tumour Total Load). The multivariate logistic analyses (OR (95% CI)) confirmed multifocality (2.16 (1.13–4.13), p = 0.019), lymphovascular infiltration (4.36 (2.43–7.82), p < 0.001) and logTTL (1.22 (1.10–1.35), p < 0.001) as independent predictors, and exhibit an AUC (95% CI) of 0.78 (0.72–0.83) with an overall fit (Hosmer–Lemeshow test) of 0.359. A change in the slope of both sensitivity and specificity is observed at about 10,000 copies/μL, without relevant changes in the Negative Predictive Values.ConclusionsUsing OSNA technique, the MI of more than 2 non-SLN can be reliably predicted.     

Predictive value of intraoperative touch preparation analysis of sentinel lymph nodes for axillary metastasis in breast cancer

BACKGROUND: Accurate intraoperative diagnosis of axillary malignancy facilitates completion axillary lymph node dissection (ALND) at the time of initial surgery. The capability to address both the primary tumor and axillary disease in a single procedure offers several advantages. This study was designed to define the predictive value of intraoperative touch preparation analysis of sentinel lymph nodes for axillary metastasis in breast cancer and to evaluate the ability of the technique to facilitate accurate synchronous ALND. METHODS: A consecutive cohort of patients with breast cancer at an Army medical center underwent intraoperative touch preparation analysis of sentinel lymph nodes concordant with initial excision. Those found to have sentinel nodes positive by touch preparation analysis underwent ALND at the initial procedure. Patients with negative sentinel nodes by touch preparation analysis, but positive by final pathology, underwent subsequent ALND. Results of the touch preparation analysis were compared with the final pathology. RESULTS: Over a 16-month period, 71 consecutive patients with breast cancer underwent initial excision and touch preparation analysis of 162 sentinel lymph nodes. Final pathology confirmed axillary metastasis in 32% (23 of 71) of patients. Of these, intraoperative touch preparation analysis identified 48% (11 of 23). There were no false positives or unnecessary axillary dissections based upon touch preparation results. Per sentinel node, the positive predictive value was 100%, the sensitivity was 47%, and the specificity was 100%. On a per patient basis, the positive predictive value was 100%, and the sensitivity and specificity were 48% and 100%, respectively. CONCLUSIONS: Intraoperative touch preparation analysis is an effective adjunct to sentinel lymph node biopsy. In our series, it facilitated a definitive cancer operation at the time of initial surgery in nearly 50% of patients, and ensured that no patient underwent an unnecessary axillary dissection.     

Touch Preparation or Frozen Section for Intraoperative Detection of Sentinel Lymph Node Metastases From Breast Cancer

Background:The preferred technique for intraoperative evaluation of the sentinel lymph node has not been determined. The purpose of this study was to compare the sensitivity and accuracy of intraoperative evaluation of the sentinel lymph node by touch preparation cytology and frozen section.Methods:A total of 117 patients with clinically node-negative breast cancer or ductal carcinoma-in-situ undergoing sentinel lymph node biopsy had intraoperative evaluation of the sentinel node by touch preparation, frozen section, or both. The results of the intraoperative evaluation were compared with the final histological results of hematoxylin and eosin (H&E) paraffin section and immunohistochemistry (IHC).Results:Twenty-six (57%) of the 46 patients with nodal involvement had metastases detected during surgery. The sensitivity of touch preparation for detecting macrometastases was 78%; for detecting all H&E metastases, including micrometastases, was 57%; and for detecting all metastases, including those seen on IHC, was 40%. The sensitivity of frozen section for detecting macrometastases was 83%; for detecting all H&E metastases, including micrometastases, was 78%; and for detecting all metastases, including those seen on IHC, was 64%. Both have a low sensitivity for micrometastases seen by H&E paraffin section: 57% and 78%, respectively. Neither detected micrometastases diagnosed by IHC only.Conclusions:Both touch preparation and frozen section seem to be accurate in detecting macrometastases, but not micrometastases. Intraoperative evaluation of the sentinel lymph node by touch preparation allows for a quick evaluation of the node without wasting significant tissue and without detecting occult microscopic metastases, which may be beneficial because the clinical importance of these has yet to be elucidated.     

Predictors of nonsentinel lymph node metastasis in breast cancer patients

BACKGROUND: In order to define a future subset of breast cancer patients in whom the axilla may be staged by sentinel lymph node biopsy alone, the conditions under which nonsentinel axillary lymph node metastases occur must be delineated. METHODS: A prospective database including 212 breast cancer patients who underwent sentinel lymph node biopsy followed by completion axillary dissection at our institution was reviewed. A multivariate, logistic, stepwise regression was performed to evaluate the relationship between nonsentinel lymph node metastasis and patient age, primary tumor size, presence of lymphatic invasion, use of radioisotope to identify the sentinel node and degree of metastasis in the sentinel node. RESULTS: Tumor size greater than 2 cm, lymphatic invasion of the primary tumor, macrometastasis in the sentinel node, and use of radioisotope all positively correlated independently with metastasis in the nonsentinel lymph node (P = 0.0001, P = 0.0483, P = 0.0008, P = 0.0271, respectively). CONCLUSIONS: Predictors of nonsentinel axillary node metastasis exist and are important in defining those patients in whom a sentinel lymph node biopsy alone may not be adequate.