Intraoperative Evaluation Of Sentinel Lymph Nodes Research Articles

Intraoperative evaluation of sentinel lymph nodes in patients with breast cancer treated with systemic neoadjuvant therapy

AimsTouch preparation (TP) and frozen section (FS) are the two methods routinely used in the intraoperative evaluation (IOE) of sentinel lymph nodes (SLNs) to detect metastases in patients with breast...

Update on sentinel node pathology in breast cancer

Pathologic examination of the sentinel lymph nodes (SLNs) in patients with breast cancer has been impacted by the publication of practicing changing trials over the last decade. With evidence from the ACOSOG Z0011 trial to suggest that there is no significant benefit to axillary lymph node dissection (ALND) in early-stage breast cancer patients with up to 2 positive SLNs, the rate of ALND, and in turn, intraoperative evaluation of SLNs has significantly decreased. It is of limited clinical significance to pursue multiple levels and cytokeratin immunohistochemistry to detect occult small metastases, such as isolated tumor cells and micrometastases, in this setting. Patients treated with neoadjuvant therapy, who represent a population with more extensive disease and aggressive tumor biology, were not included in Z0011 and similar trials, and thus, the evidence cannot be extrapolated to them. Recent trials have supported the safety and accuracy of sentinel lymph node biopsy (SLNB) in these patients when clinically node negative at the time of surgery. ALND remains the standard of care for any amount of residual disease in the SLNs and intraoperative evaluation of SLNs is still of value for real time surgical decision making. Given the potential prognostic significance of residual small metastases in treated lymph nodes, as well as the decreased false negative rate with the use of cytokeratin immunohistochemistry (IHC), it may be reasonable to maintain a low threshold for the use of cytokeratin IHC in post-neoadjuvant cases. Further recommendations for patients treated with neoadjuvant therapy await outcomes data from ongoing clinical trials. This review will provide an evidence-based discussion of best practices in SLN evaluation.

Intraoperative sentinel lymph node evaluation in patients with node-positive breast cancer status post neoadjuvant systemic therapy - An institutional experience

Recent studies have shown the feasibility and utility of sentinel lymph node (SLN) biopsy in patients with biopsy proven node-positive breast cancer after neoadjuvant chemotherapy. We reviewed our experience in intraoperative SLN evaluation in such cases and its effect on axillary management. A retrospective analysis of breast cancer patients (2015–2018) with a biopsy-proven positive axillary lymph node, who received neoadjuvant systemic therapy and underwent intraoperative SLN assessment was performed. Intraoperative SLN assessment results were compared with final pathology. Its accuracy and effect on axillary management is summarized. We identified 106 patients with positive axillary lymph node and neoadjuvant systemic therapy between the ages of 28 and 75 years who had SLN biopsy and lumpectomy (33) or mastectomy (73). Three or more SLNs were identified in 91 cases (86 %). The previously biopsied lymph node was identified as one of the sentinel lymph nodes in 93 cases (88 %). There is a high concordance rate between frozen section diagnosis and final diagnosis on sentinel lymph nodes. No false positive case and seven false negative frozen section diagnosis cases (diagnosed as negative on frozen section and positive on permanent sections) were identified. False-negative frozen section diagnosis correlated with low-volume nodal disease and obscuring tumor bed changes. Almost half of the positive lymph nodes were converted to negative after neoadjuvant chemotherapy. SLN biopsy with intraoperative frozen section evaluation after neoadjuvant systemic therapy in node-positive patients is an effective way to minimize axillary surgery.

Long-term follow up after sentinel node biopsy alone for early-stage cervical cancer

ObjectiveSentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy. MethodsWe performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed. ResultsThe median age of the patients was 34 years (range, 21–73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25–145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate. ConclusionsSNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate.

Intraoperative Molecular Analysis of Total Tumor Load in Sentinel Lymph Node: A Predictor of Axillary Status in Early Breast Cancer.

Background:Axillary lymph node dissection (ALND) remains the standard of care in breast cancer patients with positive sentinel lymph node (SLN). However, approximately 40–60% of patients with positive SLNs have not developed to non-SLN metastasis and ALND seems to be an overtreatment. The purpose of this study was to analyze predictors and define a specific cut-off of total tumor load (TTL) of CK19 that can be used as a predictive factor of non-SLN metastasis in early breast cancer patients.Materials and Methods:The records of 238 patients with cT1-3N0 breast cancer who had an intraoperative SLN evaluation performed through One-Step nucleic acid (OSNA) assay at Songklanagarind Hospital between 1 January 2015 and 31 December 2019 were examined. Univariate and Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict metastasis to non-SLNs. Finally, receiver operative characteristics (ROC) curves were used to choose an optimal TTL cut-off value. Results:Of a total of 110 patients who had a positive SLN, only 48 (43.64%) were found to have positive nodes in non-SLN. Multivariate analysis revealed that lymphovascular invasion, type of SLN metastasis and SLN TTL (copies/μL) were independent predictors of positive non-SLNs. TTL cut-off value was 19,000 copies/μL, with an AUC of 0.838 with 72.7% sensitivity and 84.7% specificity to predict non-SLN metastasis. Conclusions:The likelihood of positive non-SLNs in patients who showed a positive SLN correlates with lymphovascular invasion, type of SLN metastasis and SLN TTL (copies/μL). Our result revealed that the patients with a SLN TTL ≥19,000 copies/µl continue to attract the recommendation to proceed with ALND. This cut-off value can then help clinicians to assess which patients would benefit from ALND.

Quality assurance review: Intra-operative evaluation of sentinel lymph nodes in breast cancer.

BackgroundIntraoperative consultation (IOC) of axillary sentinel lymph node (SLN) biopsy continues to play a role in selected breast cancer patients. The reported sensitivity rates for intraoperative SLN evaluation in breast cancer range from 47% to 80%. We study a center where the majority of SLN IOC is performed by imprint cytology, and a protocol was established to limit microscopic examination to three slides for a reporting TAT goal of 30 min.MethodsApproval to conduct this study was obtained from the REB. A retrospective review was performed on all consecutive SLN cases sent for IOC. Reported IOC assessments of all cases were compared with the final pathology.ResultsOf 164 patients, there were 22 (13%) false negative IOC events, including 15 missed macro‐metastasis and 7 missed micro‐metastasis. The overall sensitivity for touch imprint in detecting SLNs macro‐metastasis was 70.9%. Reporting total turnaround time was on average 3 min longer, whereas sensitivity and specificity were not significantly different in the two protocol periods.ConclusionImplementation of an IOC policy for a maximum of three slides for imprint cytology did not result in a significant impact on the sensitivity, specificity, or total turnaround time for SLN in breast cancer patients. False negative IOC events were mainly due to sampling error. Quality review was made difficult by limited documentation related to the gross handling of the specimens at IOC. System factors identified include insufficient space for the IOC report on the pathology requisition, and the lack of clearly communicated expectations for documentation.

Sentinel lymph node intraoperative analysis in endometrial cancer.

Surgical staging in endometrial cancer has evolved and sentinel lymph node (SLN) mapping has replaced a full pelvic and paraaortic lymphadenectomy in several cases. An intraoperative evaluation of SLN might identify patients who could benefit the most from a full lymphadenectomy. The aim of this study is to evaluate the clinical relevance of frozen section of SLN. A retrospective analysis in patients with endometrial cancer who underwent SLN mapping with intraoperative evaluation at frozen section between February 2016 and September 2019 was performed. In case of metastatic involvement, a full lymphadenectomy was performed. Fifty-eight patients met the inclusion criteria. Clinical-pathologic characteristics of the patients and surgical data were analyzed. Overall, bilateral and unilateral detection rates were 100% (58/58), 89.7% (52/58), and 10.3% (6/58), respectively. Eight patients had a stage IIIC disease at permanent section. Frozen section detected SLN metastases in four of eight patients. Of these, two were micrometastases and two were macrometastases. At frozen section of the SLNs, no macrometastases were misdiagnosed. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of frozen section in detecting metastases was 50%, 100%, 93%, 100% and 92.6%, respectively. The intraoperative evaluation of SLN in endometrial cancer accurately identifies patients with macrometastases. This is the cohort that might benefit the most of a full lymphadenectomy for a higher risk of additional lymph node metastases.

The value and practical utility of intraoperative touch imprint cytology of sentinel lymph node(s) in patients with breast cancer: A retrospective cytology-histology correlation study.

Objective:Intraoperative evaluation of sentinel lymph nodes (SLNs) for patients with breast cancer is widely performed with frozen section (FS), cytology, or a combination of both. Touch imprint cytology (TIC) reportedly has an equivalent sensitivity to FS. We studied its diagnostic utility to detect SLN metastases.Materials and Methods:Cases of 367 patients with breast cancer who underwent intraoperative valuation of SLNs (507 LNs) were evaluated. All FS and corresponding TIC slides of SLNs of each case were reviewed microscopically for the presence of metastases of any size. If present, the metastatic focus was measured on the FS.Results:Of these 507 SLNs, 82 LNs (16.2%) from 69 women were found to have metastases in the FS and consisted of 5 LNs of isolated tumor cells, 15 of micrometastasis, and 62 of macrometastasis. TIC identified metastases in 69 of these 82 SLNs (sensitivity: 84.1%, specificity: 100%, and accuracy: 97.4%). All macrometastases could be detected by TIC, whereas TIC identified approximately 50% of micrometastases and none of isolated tumor cells. The size detection limit of metastatic foci, defined as the smallest dimension of metastasis detected without false negatives, was 2 mm. The smallest metastatic focus identified was 0.8 mm.Conclusions:TIC of SLNs is of great use given its negative predictive value of 100% for identification of macrometastasis in our study. For intraoperative evaluation of SLNs, based on our data, a practical two-step approach is proposed: SLN evaluation should be initially performed by TIC and then proceed to FS histological analysis only when cytologically positive to determine the size of metastatic focus.

Abstract OT3-01-02: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study

Abstract Introduction Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients with negative SLNs without jeopardizing survival or regional control. International guidelines keep recommending ALND in the presence of positive (+) SLNs. However SLN is the only site of axillary metastasis (MTS) in many cases (60%). Retrospective studies have also shown a low risk of locoregional relapse in patients with SLNs+ not receiving ALND.This latter finding was recently confirmed in a randomized trial comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+. However the observation of both similar relapse rate and survival in the 2 arms and the conclusion of a non-inferiority of SLNB compared to ALND require cautiousness because of some study limitations: premature enrollment cessation due to death rate lower than expected, short follow-up (6 years), small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (>90%) which irradiates the breast but also the I° axillary level, thereby contributing to the low rate of regional relapse in the SLNB arm due to lymph node sterilization. Consequently further randomized trials with more precise selection criteria based on homogeneous clinico-pathological features and with longer follow-up are needed to confirm that performing only SLNB does not affect survival or relapse risk in patients with 1-2 SLNs+. Materials and Methods Primary and secondary aims of the present 2-arm randomized trial are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse, respectively, thus evaluating whether SLNB is or is not inferior to ALND. Patients receive either conservative surgery or mastectomy and radiotherapy. They all undergo intraoperative SLNB and SLN evaluation, and are randomly assigned to either further dissection of level I-II axillary lymph nodes (standard ALND arm) or absence of any axillary surgery (experimental SLNB arm). According to International Guidelines post-surgery treatments. Eligibility criteria are: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 SLNs presenting macroMTS at intraoperative or definitive histological evaluation; no distant MTS; no neoadjuvant therapy; no previous invasive BC, signed informed consent. Exclusion criteria are: in situ, inflammatory, contralateral BC; presence of only microMTS in the SLN+; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. Follow-up controls foresee: clinical examination every 6 months for 5 years and yearly thereafter; annual mammography and breast echography; annual axillary echography for patients in the SLNB arm; additional laboratory and instrumental surveys in case of suspected onset of distant MTS. The primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and to locoregional (ipsilateral breast or axillary, internal mammary or sopraclaveolar lymph nodes) disease recurrence. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Citation Format: Corrado Tinterri, Emilia Marrazzo, Federico Frusone, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-02.

Role of gamma probe-assisted intraoperative sentinel lymph node evaluation in predicting axillary breast cancer metastasis after neoadjuvant chemotherapy.

Intraoperative sentinel lymph node biopsy is a universally accepted technique to identify patients who are candidates for axillary lymph node dissection during breast cancer surgery. However, there is controversy over its use in patients who underwent preoperative neoadjuvant chemotherapy. This study aimed to examine the diagnostic value of gamma probe-assisted intraoperative sentinel lymph node examination with frozen section in breast cancer patients who had undergone preoperative neoadjuvant chemotherapy. This retrospective study included 94 tumors diagnosed with stage IIA, IIB or IIIA invasive breast cancer with locoregional lymph node metastasis who underwent surgical treatment after neoadjuvant chemotherapy. Intraoperatively, axillary sentinel lymph node sampling was done using radioactive colloid and gamma probe and materials were examined with frozen section method. Patients with positive sentinel nodes underwent axillary resection. Histopathological examination of all surgical samples was done postoperatively. In 87 of 94 tumors (92.6%), a sentinel lymph node could be identified using the method. The sensitivity, specificity and accuracy of the method for predicting axillary macro metastasis were 85.7, 86.5 and 86.2%, respectively, with 5.7% false negative rate. Sentinel lymph node identification using preoperative scintigraphy and intraoperative use of gamma probe seems to be a feasible and efficient method in terms of differentiating patients that require axillary lymph node dissection during breast cancer surgery, even when they have received neoadjuvant chemotherapy. Further large prospective studies allowing subgroup analyses are warranted.

Intraoperative imprint cytology of sentinel lymph nodes in breast cancer patients: Comparation with frozen section

Background/Aim. Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes. Intraoperative assessment of sentinel lymph nodes might be done by frozen section (FS), touch imprint cytology (TIC) and one step nucleic acid amplification. The aim of this study was to review our institution's results with SLN biopsy using TIC and FS technique as intraoperative diagnostic tool for breast cancer patients. Methods. SLNs from 101 patients were examined intraoperatively by frozen hematoxylin-eosin (H&E) stain and by touch imprint cytology. Results of TIC were compared with FS and permanent histology sections. Results. The total number of dissected SLNs was 163 with a mean of 1.6 (1?4) per patient. The permanent H&E identified 19 (19%) patients with a sentinel lymph node metastasis and 82 (81%) patients with tumor-free sentinel nodes. The sensitivity/ specificity rates were 73.7%/99.3%, respectively for TIC and 84.2%/100%, respectively for FS. Relevant positive/ negative predictive values were 93.3%/96.6%, respectively for TIC and 100%/97.9%, respectively for FS. Conclusion. Our experience with TIC and FS for the intraoperative evaluation of SLNs is similar to the findings from previously reported studies. We detected the high specificity for both methods, but TIC technique appeared to be less sensitive than FS in detecting SLN metastases in breast cancer patients. TIC could be recommended as reasonable alternative to frozen section due to its simplicity and low cost.

Abstract P3-03-16: Intraoperative evaluation of sentinel lymph nodes after neoadjuvant systemic therapy in breast cancer

Abstract Introduction: Intraoperative evaluation of sentinel lymph nodes (SLN) in breast cancer patients are performed using Touch preparation (TP) and/or frozen section (FS). Touch preparation for intraoperative evaluation of SLN is quick and known to be a highly sensitive and specific method for detection of metastasis. Detecting metastases in SLN intraoperatively can be challenging in patients who receive neoadjuvant systemic therapy (NST). In our hospitals, we have been routinely evaluating SLN intraoperatively in patients who have undergone (NST), including those with known metastasis to an axillary lymph node (LN) prior to therapy. Objective: To compare the sensitivity and specificity of TP and frozen section (FS) in the intraoperative evaluation of SLN in the neoadjuvant setting. Material and Methods: This retrospective review study was approved by the institutional review board. Four hundred ninety-eight SLN from 142 patients were included in this study. The intraoperative results for TP and FS were compared with the final pathology results. Relevant clinical and pathological findings such as type of surgery, tumor grade, histologic subtype, and size of metastasis were reviewed. Results: Of the 498 SLN evaluated intraoperatively, 341 were by TP only, 57 by FS only and 100 by both. Of the 341 SLN examined by TP only, 313 (92%) were interpreted as negative and 28 (8%) as positive for carcinoma intraoperatively. Eighteen LN turned out to be false negative (FN) with no false positives (FP) (sensitivity=62%, specificity=100%). In the false negative cases, 12 LN had micrometastasis, 6 macrometastasis and 1 showed isolated tumor cells (ITC). The size of the macrometastatic ranged from 3 mm to 10 mm. Of the 57 LN examined by FS only, 48 were true negative and 9 were true positive (sensitivity=100%, specificity=100%). Of the 100 LN evaluated by both TP and FS, 59 were interpreted as negative and 41 as positive for carcinoma. There were 8 false negatives and 1 false positive (sensitivity=83%, specificity=98%). Of the 8 false negatives, 7 showed micrometastasis and 1 LN had ITC. Discussion: In neoadjuvant cases, both the primary tumor as well as lymph node metastases can show therapy effect such as fibrosis, necrosis and/or histiocytic aggregates. Evaluating SLN in NST cases can be challenging secondary to these effects. The TP slides are often paucicellular in SLN with treatment effect. Residual tumor cells are often trapped in a fibrotic scar and do not transfer onto the TP slide leading to low sensitivity. Therefore, for optimal intraoperative evaluation of SLN in NST cases, frozen section with or without touch preparation, is recommended. Citation Format: Sahoo S, Mir M, Sarode V, Fang Y, Peng Y, Gwin K, Hwang H. Intraoperative evaluation of sentinel lymph nodes after neoadjuvant systemic therapy in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-16.

Intraoperative sentinel lymph node evaluation: Optimizing surgical pathology practices in an era of changing clinical management.

Axillary lymph node status is an independent prognostic indicator in breast cancer. Intraoperative identification of metastatic carcinoma in sentinel lymph nodes may allow for concurrent axillary lymph node dissection at the time of primary tumor excision. A retrospective review of patients undergoing primary breast cancer excision with sentinel lymph node sampling was performed. Sensitivity and specificity of imprint cytology (touch prep) with and without the incorporation of gross evaluation was determined using permanent section results as the gold standard. Five hundred sixteen lymph nodes were analyzed by imprint cytology in 213 patients, and 203 lymph nodes were analyzed in 74 patients incorporating gross examination. Sensitivity and specificity for the detection of macrometastases by touch prep alone were 60% and 99% respectively with 4 patients undergoing same-day axillary dissection for only micrometastatic disease. False negative causes included lack of transfer of malignant cells in 8 cases and misinterpretation of tumor cells in 6 cases. Incorporating gross examination in the modified protocol resulted in reduced sensitivity of 38%, but achieved the desired 100% specificity and positive predictive value. Imprint cytology alone did not reliably distinguish between micro- and macrometastatic disease. Gross assessment combined with imprint cytology allows for improved assessment of volume of axillary disease, but is an insensitive technique.

Factors impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer.

Sentinel lymph node dissection (SLND) is a standard axillary staging technique in breast cancer and intraoperative sentinel lymph node (SLN) assessment is important for decision-making regarding additional treatment and reconstruction. This study was undertaken to investigate clinicopathologic factors impacting the accuracy of intraoperative SLN evaluation. Records of patients with clinically node-negative, invasive breast cancer who underwent SLND with frozen section intraoperative pathologic evaluation from 2004 to 2007 were reviewed. Intraoperative SLN assessment results were compared to final pathology. Patients with positive SLNs that were initially reported as negative during intraoperative assessment were considered false negative (FN) events. Primary tumor histology, grade, receptor status, size, lymphovascular invasion (LVI), multifocality, neoadjuvant chemotherapy or hormonal therapy, number of SLNs retrieved, and SLN metastasis size were evaluated. The study included 681 patients, of whom 262 (38%) received neoadjuvant therapy. There were 183 (27%) patients who had a positive SLN on final pathology, of whom 60 (33%) had FN events. On univariate analysis, lobular histology, favorable histology, absence of LVI and micrometastasis were associated with a higher FN rate. On multivariate analysis, favorable and lobular histology and micrometastasis were independent predictors of FN events whereas LVI and receipt of neoadjuvant therapy were not statistically significant predictors. The accuracy of intraoperative SLN evaluation for breast cancer is affected by primary tumor histology and size of the SLN metastasis. There was no significant association between neoadjuvant therapy and the FN rate by intraoperative assessment. This information may be helpful in counseling patients about their risk for a FN intraoperative SLN assessment and for planning for immediate breast reconstruction in patients undergoing mastectomy.

The Pre-Treatment Neutrophil-Lymphocyte Ratio: a Useful Tool in Predicting Non-Sentinel Lymph Node Metastasis in Breast Cancer Cases

Background:The sentinel lymph node (SLN) biopsy is a highly accurate predictor of overall axillary nodal status in early breast cancer patients. There is however, still a debate on which patients with a positive SLN can benefit from axillary lymph node dissection (ALND). Numerous studies have been designed to identify variables that are predictive of non-SLN metastasis to avoid a complete ALND. The aim of this study was to determine whether the pre-treatment neutrophil-lymphocyte ratio (NLR) can be a predictive factor of non-SLN metastasis in early breast cancer patients.Materials and Methods:The records of 214 consecutive patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation at Songklanagarind Hospital between the 1st of March 2011 and the 30th of May 2016 were examined. Data on patient demographics, tumor variables and NLR were collected and factors for non-SLN metastasis were analyzed using multivariate logistic regression. The power of the NLR was quantified with receiver operating characteristics (ROC) curves as measured by the areas under curves (AUC).Results:Multivariate analysis established presence of lymphovascular invasion (OR 8.4, 95%CI 2.3-31.3, p=0.002), macrometastasis (OR 6.6, 95%CI 1.8-24.7, p=0.005), and NLR (OR 2.3, 95%CI 1.1-4.8, p=0.033) as predictive factors of non-SLN metastasis with statistical significance. The AUC for NLR was 0.7 (95%CI 0.6-0.8) with an optimal cut-off of 2.6 giving a sensitivity of 62%, a specificity of 83.8%, a positive predictive value of 77.3% and a negative predictive value of 70.5%.Conclusion:Pre-treatment NLR is a useful diagnostic aid for predicting additional non-SLN metastasis.

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.

Decline in Frozen Section Diagnosis for Axillary Sentinel Lymph Nodes as a Result of the American College of Surgeons Oncology Group Z0011 Trial.

-Results of the American College of Surgeons Oncology Group Z0011 trial showed that patients with early-stage breast cancer and limited sentinel node metastasis treated with breast conservation and systemic therapy did not benefit from axillary lymph node dissection. Subsequently, most pathology departments have likely seen a decrease in frozen section diagnosis of sentinel lymph nodes. -To determine the effect of the Z0011 trial on pathology practice and to examine the utility of intraoperative sentinel lymph node evaluation for this subset of patients. -Pathology reports from cases of primary breast cancer that met Z0011 clinical criteria and were initially treated with lumpectomy and sentinel lymph node biopsy from 2009 to 2015 were collected. Clinicopathologic data were recorded. -Sentinel lymph node biopsies sent for frozen section diagnosis occurred in 22 of 22 cases (100%) in 2009 and 15 of 22 cases (68%) in 2010 during the pre-Z0011 years, and in 3 of 151 cases (2%) collected in 2011 through 2015, considered to be post-Z0011 years. Of the 151 post-Z0011 cases, 28 (19%) had sentinel lymph nodes with metastasis, and 147 (97%) were spared axillary lymph node dissection. -Following Z0011, intraoperative sentinel lymph node evaluation has significantly decreased at our institution. Prior to surgery, all patients had clinically node-negative disease. After sentinel lymph node evaluation, 97% (147 of 151) of the patients were spared axillary lymph node dissection. Therefore, routine frozen section diagnosis for sentinel lymph node biopsies can be avoided in these patients.

The Role of Sentinel Lymph Node Biopsy in the Management of Breast Cancer

The sentinel lymph node (SLN) is defined as the first node(s) receiving lymphatic drainage from a primary tumour. A promising alternative to axillary lymph node dissection (ALND) is sentinel lymph node biopsy. SLN biopsy has been introduced as a technique to identify axillary lymph node most likely to contain tumour cells metastasizing from a primary carcinoma of breast. Several methods of identifying the SLN exists, including the use of radioactive tracer, lymphazurin dye or combination of the two via intraparenchymal and/or intradermal, peritumoral or periaerolar injection sites. Intraoperative evaluation of SLNs are done by performing FS(Frozen Section) on all the lymph nodes after serially sectioning them at 3-4mm intervals; at least 2 levels are cut of all the sentinel lymph nodes. In addition, touch preparation cytology(TP) smear may also be made for evaluation. The limitations of SLNB is that a proportion of patients who have metastasis limited to the SLN can be predicted when there is a combination of tumour size <1.0cm, the absence of lymphovascular invasion and micrometastatic disease (<0.2cm) in SLN. However for patients with large breast cancer, the role of SLNB is controversial. Early studies of SLNB in large breast cancer patients demonstrated a high (8-18%) false negative rate, with the accuracy worsening with the increasing size. Excision of SLNs have an extremely low morbidity and a high degree of staging accuracy. A tumour-free SLN virtually excludes lymphatic involvement of the entire regional lymphatic basin. More than 50 observational studies of SLNB validated by a back up ALND demonstrate that SLNB is feasible, accurate and suitable for virtually all patients with operable clinically node negative disease. Sentinel lymph node biopsy not only provide prognostic information, but also aims to guide adjuvant therapy without the untoward side effects of complete axillary dissection.J Bangladesh Coll Phys Surg 2014; 32: 211-217

A prospective comparison of molecular assay and touch imprint cytology for intraoperative evaluation of sentinel lymph nodes.

Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissections during the same operation, reducing the need for a second operation. The present study aimed to prospectively compare the GeneSearch(TM) Breast Lymph Node (BLN) Assay with touch imprint cytology (TIC) for intraoperative evaluation of SLNs. SLNs were sectioned in 1.5 - 3.0 mm pieces. TIC was performed on all pieces and the BLN Assay and postoperative histology evaluations were performed on different alternating node pieces. Overall performance of the BLN Assay was compared with that of TIC relative to the postoperative histology results. A total of 90 patients enrolled in the study. Complete intraoperative data for both the BLN Assay and TIC were collected in 86 patients. The sensitivity, specificity, and overall accuracy of the BLN Assay were 82%, 97%, and 92%, respectively on a per patient basis compared with those of TIC which were 67%, 100%, and 90%. Performance of the BLN Assay was superior to that of TIC and the additional application of TIC did not help improve the total sensitivity and accuracy of the intraoperative assessment. The existence of ectopic breast tissue might be a possible cause of false positive for the BLN assay. In addition, the BLN Assay complements histopathology assessment and can minimize sampling error without increasing pathologists' workload.

One-Step Nucleic Acid Amplification in Breast Cancer Sentinel Lymph Node: A Single Institutional Experience and a Short Review.

Sentinel lymph node (SLN) examination is a standard in breast cancer patients, with several methods employed along its 20 years history, the last one represented by one-step nucleic acid amplification (OSNA). The latter is a intra-operative molecular assay searching for CK19 mRNA as a surrogate of metastatic cells. Our 3 years experience with OSNA (1122 patients) showed results overlapping those recorded in the same institution with a morphological evaluation (930 patients) of SLN. In detail, the data of OSNA were almost identical to those observed with standard post-operative procedure in terms of patients with positive SLN (30%) and micrometastatic/macrometastatic involvement of SLN (respectively, 38–45 and 62–55%). By contrast, when OSNA was compared to the standard intraoperatory procedure, it was superior in terms of accuracy, prompting the use of this molecular assay as a very valid, and reproducible for intra-operative evaluation of SLN. Further possibilities prompting the use of OSNA range from adhesion to quality control programs, saving of medical time, ability to predict, during surgery, additional nodal metastasis, and molecular bio-banking.