Assessment Of Sentinel Lymph Nodes Research Articles

A multicentre validation of Metasin: a molecular assay for the intraoperative assessment of sentinel lymph nodes from breast cancer patients

Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs. RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB). Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.

Ex Vivo Assessment of Sentinel Lymph Nodes in Breast Cancer Using Shear Wave Elastography.

Axillary lymph node status is one of the important prognostic factors in early-stage breast cancer. Despite the combined use of sonography, fine-needle aspiration, and sentinel lymph node (SLN) dissection, there is a gap between the potential effectiveness of those techniques and current success to determine the axillary lymph node status. The main aim of this study was to evaluate the baseline accuracy of shear wave elastography for differentiation of benign versus malignant SLNs in an ex vivo artifact-free environment. Thirty patients with breast cancer scheduled for SLN dissection were enrolled prospectively after informed consent and Institutional Review Board approval were obtained. After dissection, lymph nodes were embedded in ultrasound gel and examined with grayscale sonography and shear wave elastography. Findings were compared to histopathologic results. A total of 64 SLNs obtained from the 30 patients were evaluated. Twelve of them (18.8%) were metastatic, and 52 (81.2%) were benign. The mean cortical thickness (benign versus metastatic, 1.6 versus 4.4 mm), short-axis length (4.63 versus 7.50 mm), cortical stiffness (10.7 versus 25.5 kPa), and hilar stiffness (7.5 versus 11.3 kPa) were statistically higher in metastatic lymph nodes (P ≤ .02). Area under the receiver operator characteristic curve values for these variables were 0.814, 0.768, 0.786, and 0.759, respectively. Cortical thickness was found to have the highest diagnostic performance, followed by cortical stiffness. Shear wave elastography can be used with grayscale sonography for evaluation of cases to decide on needle biopsy sampling. However, it cannot be used as a replacement for fine-needle aspiration or SLN dissection.

99mTc-Nanocolloid SPECT/MRI Fusion for the Selective Assessment of Nonenlarged Sentinel Lymph Nodes in Patients with Early-Stage Cervical Cancer.

We aimed to explore the accuracy of (99m)Tc SPECT/MRI fusion for the selective assessment of nonenlarged sentinel lymph nodes (SLNs) for diagnosing metastases in early-stage cervical cancer patients. We consecutively included stage IA1-IIB1 cervical cancer patients who presented to our tertiary referral center between March 2011 and February 2015. Patients with enlarged lymph nodes (short axis ≥ 10 mm) on MRI were excluded. Patients underwent an SLN procedure with preoperative (99m)Tc-nanocolloid SPECT/CT-based SLN mapping. When fused datasets of the SPECT and MR images were created, SLNs could be identified on the MR image with accurate correlation to the histologic result of each individual SLN. An experienced radiologist, masked to histology, retrospectively reviewed all fused SPECT/MR images and scored morphologic SLN parameters on a standardized case report form. Logistic regression and receiver-operating curves were used to model the parameters against the SLN status. In 75 cases, 136 SLNs were eligible for analysis, of which 13 (9.6%) contained metastases (8 cases). Three parameters-short-axis diameter, long-axis diameter, and absence of sharp demarcation-significantly predicted metastatic invasion of nonenlarged SLNs, with quality-adjusted odds ratios of 1.42 (95% confidence interval [CI], 1.01-1.99), 1.28 (95% CI, 1.03-1.57), and 7.55 (95% CI, 1.09-52.28), respectively. The area under the curve of the receiver-operating curves combining these parameters was 0.749 (95% CI, 0.569-0.930). Heterogeneous gadolinium enhancement, cortical thickness, round shape, or SLN size, compared with the nearest non-SLN, showed no association with metastases (P= 0.055-0.795). In cervical cancer patients without enlarged lymph nodes, selective evaluation of only the SLNs-for size and absence of sharp demarcation-can be used to noninvasively assess the presence of metastases.

The role of sentinel lymph nodes in endometrial and cervical cancer.

Sentinel lymph node assessment aims to determine lymphatic spread while preventing unnecessary interventions and morbidity for those who will not benefit from lymphadenectomy. All detection methods have demonstrated reasonable sensitivity with a low false negative rate and high negative predictive value; as long as the surgeon removes all enlarged lymph nodes and a site-specific lymphadenectomy is performed if there is no mapping. The significance of micrometastases and long term outcomes are yet to be determined.

Sentinel lymph node assessment in breast cancer patients receiving neo‐adjuvant chemotherapy: to biopsy before or after?

Keywords: breast cancer; sentinel node biopsy; neo-adjuvant chemotherapy; false-negative; axillary lymph node dissection

The efficacy and efficiency of half frozen section assessment of breast cancer sentinel lymph nodes: A retrospective analysis of 1116 cases.

1055 Background: Sentinel lymph node (SLN) biopsy became the standard of care for the staging of clinically negative axillary lymph node in patients with invasive breast cancer. Surgeons often requ...

Impact of delayed lymphoscintigraphy for sentinel lymphnode biopsy for breast cancer

Despite universal adoption of sentinel lymph node biopsy (SLNB) for breast cancer, there remains no standardized protocol for preoperative lymphoscintographic assessment of sentinel nodes. Both immediate and delayed lymphoscintigraphy are currently utilized, although it is unclear how delayed imaging impacts SLN identification. Among patients diagnosed with breast cancer who underwent SLNB at Duke from 2011 to 2012, two protocols for preoperative lymphoscintigraphy were used: protocol A included both immediate and delayed lymphoscintigraphy (n = 152), while protocol B involved immediate lymphoscintigraphy only (n = 103). The overall intraoperative SLN identification rate was 98.4% and did not differ between groups. A lower number of SLN were visualized on the immediate scan using protocol A compared to protocol B (P < 0.001). Although a greater total number of nodes was excised using protocol A, this result was not statistically significant (P = 0.08). Moreover, there was no significant difference in the number of negative SLN between groups (P = 0.51). We found no significant impact on identification rate or number of SLN excised with the use of delayed versus immediate imaging. These findings support abandoning delayed lymphoscintographic imaging, except in those cases where aberrant drainage is suspected.

P043. Specialist Masters Degree in Oncoplastic Breast Surgery: An update of student engagement and feedback

P043. Specialist Masters Degree in Oncoplastic Breast Surgery: An update of student engagement and feedback

P042. One Step Nucleic Acid Amplification copy number as a predictor for non-sentinel lymph node positivity

Introduction: OSNA (One-Step Nucleic Acid Amplification) is an established technique for intra-operative assessment of sentinel lymph node (SLN) metastasis, used in 26 hospitals in the UK. The Z0011 and AMAROS trials prompted controversy over whether axillary lymph node dissection (ALND) should be performed at all. Currently we use a CK19 copy number of > 5000 (macrometastasis) to identify patients requiring ALND. We investigated whether a higher copy number of 7700 is a better predictor of non-sentinel lymph node (NSLN) positivity.

P094. Clinical feasibility of Cerenkov Luminescence Imaging (CLI) for intraoperative assessment of tumour excision margins and sentinel lymph node metastases in breast-conserving surgery

P094. Clinical feasibility of Cerenkov Luminescence Imaging (CLI) for intraoperative assessment of tumour excision margins and sentinel lymph node metastases in breast-conserving surgery

Utility of intraoperative frozen section of the inguinofemoral sentinel lymph node in vulvar cancer: A retrospective cohort

Objectives: To evaluate the utility of frozen section for the intraoperative assessment of sentinel lymph nodes in vulvar cancer. Methods: A total of 131 patients with vulvar cancer were treated at the University of Tennessee—West Cancer Center over a six-year period. A total of 110 were eligible for evaluation and 65 met inclusion and exclusion criteria. The clinical records were reviewed for patient demographics, disease characteristics, sentinel lymph node eligibility, surgical and pathologic variables, and follow-up status. Results: A total of 32 of the 65 eligible patients underwent sentinel lymph node detection. No significant differences in characteristics were found between the cohorts. The sentinel lymph node detection rate was 90.6% (95% CI: 75.0% - 98.0%). Sentinel lymph node was sent for frozen section in 30 patients and 5 patients were identified to have a positive SLN (16.7%). The frozen pathology results and final pathology had a 100% correspondence of both positive and negative node results. No difference in progression-free or overall survival was observed between those who underwent sentinel detection and those who did not. Download : Download high-res image (70KB) Download : Download full-size image Conclusions: Intraoperative frozen section is an appropriate means to assess node status at the time of initial surgery, decreasing the incidence of reoperation by identifying those patients who warrant immediate complete inguinal-femoral lymph node dissection.

Adherence to a standard algorithm results in high negative predictive value of sentinel lymph node assessment using indocyanine green (ICG) and isosulfan blue (ISB) dyes in endometrial cancer

Adherence to a standard algorithm results in high negative predictive value of sentinel lymph node assessment using indocyanine green (ICG) and isosulfan blue (ISB) dyes in endometrial cancer

Utility of SPECT/CT scan for anatomical localization of pararectal and presacral sentinel nodes in prostate cancer

AimThis study has aimed to evaluate the added value of SPECT-CT scan in the preoperative assessment of sentinel nodes of the presacral and pararectal regions localized outside the standard area of extended pelvic lymphadenectomy for the staging of the pelvis in prostate cancer. SPECT-CT scan can serve as a guide for the excision of these nodes by lymphadenectomy by open surgery or laparoscopy. Materials and methodsWe evaluated 4 patients with prostate cancer presenting sentinel nodes in the pararectal and presacral regions on SPECT-CT scan performed in addition to lymphoscintigraphy. These patients underwent lymphadenectomy with robot-assisted laparoscopy together with prostatectomy. All of the excised lymph nodes were sent for histopathology study. ResultsAn average of 6 sentinel nodes per patient were found on SPECT-CT scan with a mean of 2 sentinel nodes in presacral/pararectal region. Lymphadenectomy including these areas was performed. Pararectal/presacral sentinel nodes of all patients depicted by SPECT-CT scan were tumor-free on histopathology study. Sentinel nodes (no pararectal/presacral) were positive for malignancy in only one patient. ConclusionPreoperative SPECT-CT scan is a useful tool to localize the sentinel nodes in pararectal/presacral regions. It can be an anatomic guide for new modalities of laparoscopic surgery such as robot-assisted procedures that can access the pelvic areas visualized with SPECT-CT scan, making excision of these nodes possible.

Utility of SPECT/CT scan for anatomical localization of pararectal and presacral sentinel nodes in prostate cancer

This study has aimed to evaluate the added value of SPECT-CT scan in the preoperative assessment of sentinel nodes of the presacral and pararectal regions localized outside the standard area of extended pelvic lymphadenectomy for the staging of the pelvis in prostate cancer. SPECT-CT scan can serve as a guide for the excision of these nodes by lymphadenectomy by open surgery or laparoscopy. We evaluated 4 patients with prostate cancer presenting sentinel nodes in the pararectal and presacral regions on SPECT-CT scan performed in addition to lymphoscintigraphy. These patients underwent lymphadenectomy with robot-assisted laparoscopy together with prostatectomy. All of the excised lymph nodes were sent for histopathology study. An average of 6 sentinel nodes per patient were found on SPECT-CT scan with a mean of 2 sentinel nodes in presacral/pararectal región. Lymphadenectomy including these areas was performed. Pararectal/presacral sentinel nodes of all patients depicted by SPECT-CT scan were tumor free on histopathology study. Sentinel nodes (no pararectal/presacral) were positive for malignancy in only one patient. Preoperative SPECT-CT scan is a useful tool to localize the sentinel nodes in pararectal/presacral regions. It can be an anatomic guide for new modalities of laparoscopic surgery such as robot-assisted procedures that can access the pelvic areas visualized with SPECT-CT scan, making excision of these nodes possible.

150. Scope for intra-operative sentinel lymph node assessment with one step nucleic acid amplification (OSNA) for CK19 messenger RNA in the light of American College of Surgical Oncology Group (ACOSOG) ZOO11 Trial, in an average District General Hospital in the UK

150. Scope for intra-operative sentinel lymph node assessment with one step nucleic acid amplification (OSNA) for CK19 messenger RNA in the light of American College of Surgical Oncology Group (ACOSOG) ZOO11 Trial, in an average District General Hospital in the UK

Assessment of suitability of the one step nucleic acid amplification (OSNA) assay as an intraoperative procedure for detection of metastasis in sentinel lymph nodes of breast cancer

AimWe aimed to assess the one step nucleic acid amplification (OSNA) assay as an intraoperative method in comparison with frozen sections (FS) for detection of metastasis in sentinel lymph nodes...

Can Intraoperative Sentinel Lymph Node Biopsy be Safely Avoided in Patients with Cytologically Negative Axilla?

Introduction: The importance of intraoperative sentinel lymph node biopsy in breast cancer patients has come into question after the results of the Z11 trial, which demonstrated no benefit in local or regional control with completion axillary lymph node dissection (ALND) in patients with one or two positive sentinel nodes. Previous studies have shown the advantages of preoperative ultrasound guided FNA for axillary staging in breast cancer. This retrospective analysis was performed to assess the need for intraoperative sentinel node evaluation in clinically node negative patients with negative ultrasound guided axillary FNA. Materials and Methods: Results from breast cancer patients from 2010 to present with negative axillary ultrasound-guided fine needle aspiration (USFNA) and subsequent surgical follow-up were reviewed (nZ67). Number of positive sentinel and non-sentinel lymph nodes, final nodal stage, and the size of the metastatic deposits was obtained. Results: Twelve of sixty-seven women in the study group demonstrated metastatic carcinoma in sentinel lymph nodes. Of these, seven cases of macrometastatic disease were identified, with two cases showing metastatic deposits in sentinel and non-sentinel nodes. Four cases revealed micrometastases, and one case showed isolated tumor cells on touch preparation only. The final pathologic stage in all cases with macrometastases was N1a. The negative predictive value for macrometastatic disease after a negative US-FNA was 89.6%. Conclusion: This study demonstrates that in patients with a cytologically negative axilla intraoperative assessment of sentinel lymph nodes shows no benefit, thereby preventing both the costly and time-consuming process of intraoperative sentinel lymph node assessment and morbidity of unnecessary axillary lymph node dissection.

Positive sentinel lymph node: the evolution of axillary surgery and intraoperative assessment of sentinel lymph nodes

SUMMARY Axillary lymph node dissection (ALND) has been the treatment for breast cancer in patients with sentinel lymph node (SLN) biopsy metastasis for prognostic information, local control and maybe for a small survival benefit. In recent years, clinicians have been questioning the need for axillary dissection in patients with positive SLN as the rate of axillary recurrences remains low when no ALND is performed in this group. Several variables incorporated in nomograms have been examined to predict axillary metastasis in patients with SLN metastasis and these nomograms have helped to determine which patients can spare the morbidity of the ALND. The combined multimodality in breast cancer treatments and the improvement in targeted therapies based in tumor biology have contributed to the low recurrence rates in early-stage breast cancer. As the multimodal treatment and the screening programs will improve, more patients with SLN metastasis will spare an ALND without compromising their oncologic outcome.

Sentinel node assessment for diagnosis of groin lymph node involvement in vulval cancer.

Vulval cancer is usually treated by wide local excision with removal of groin lymph nodes (inguinofemoral lymphadenectomy) from one or both sides, depending on the tumour location. However, this procedure is associated with significant morbidity. As lymph node metastasis occurs in about 30% of women with early vulval cancer, accurate prediction of lymph node metastases could reduce the extent of surgery in many women, thereby reducing morbidity. Sentinel node assessment is a diagnostic technique that uses traceable agents to identify the spread of cancer cells to the lymph nodes draining affected tissue. Once the sentinel nodes are identified, they are removed and submitted to histological examination. This technique has been found to be useful in diagnosing the nodal involvement of other types of tumours. Sentinel node assessment in vulval cancer has been evaluated with various tracing agents. It is unclear which tracing agent or combination of agents is most accurate. To assess the diagnostic test accuracy of various techniques using traceable agents for sentinel lymph node assessment to diagnose groin lymph node metastasis in women with FIGO stage IB or higher vulval cancer and to investigate sources of heterogeneity. We searched MEDLINE (1946 to February 2013), EMBASE (1974 to March 2013) and the relevant Cochrane trial registers. Studies that evaluated the diagnostic accuracy of traceable agents for sentinel node assessment (involving the identification of a sentinel node plus histological examination) compared with histological examination of removed groin lymph nodes following complete inguinofemoral lymphadenectomy (IFL) in women with vulval cancer, provided there were sufficient data for the construction of two-by-two tables. Two authors (TAL, AP) independently screened titles and abstracts for relevance, classified studies for inclusion/exclusion and extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used univariate meta-analytical methods to estimate pooled sensitivity estimates. We included 34 studies evaluating 1614 women and approximately 2396 groins. The overall methodological quality of included studies was moderate. The studies included in this review used the following traceable techniques to identify sentinel nodes in their participants: blue dye only (three studies), technetium only (eight studies), blue dye plus technetium combined (combined tests; 13 studies) and various inconsistent combinations of these three techniques (mixed tests; 10 studies). For studies of mixed tests, we obtained separate test data where possible.Most studies used haematoxylin and eosin (H&E) stains for the histological examination. Additionally an immunohistochemical (IHC) stain with and without ultrastaging was employed by 14 and eight studies, respectively. One study used reverse transcriptase polymerase chain reaction analysis (CA9 RT-PCR), whilst three studies did not describe the histological methods used.The pooled sensitivity estimate for studies using blue dye only was 0.94 (68 women; 95% confidence interval (CI) 0.69 to 0.99), for mixed tests was 0.91 (679 women; 95% CI 0.71 to 0.98), for technetium only was 0.93 (149 women; 95% CI 0.89 to 0.96) and for combined tests was 0.95 (390 women; 95% CI 0.89 to 0.97). Negative predictive values (NPVs) for all index tests were > 95%. Most studies also reported sentinel node detection rates (the ability of the test to identify a sentinel node) of the index test. The mean detection rate for blue dye alone was 82%, compared with 95%, 96% and 98% for mixed tests, technetium only and combined tests, respectively. We estimated the clinical consequences of the various tests for 100 women undergoing the sentinel node procedure, assuming the prevalence of groin metastases to be 30%. For the combined or technetium only tests, one and two women with groin metastases might be 'missed', respectively (95% CI 1 to 3); and for mixed tests, three women with groin metastases might be 'missed' (95% CI 1 to 9). The wide CIs associated with the pooled sensitivity estimates for blue dye and mixed tests increased the potential for these tests to 'miss' women with groin metastases. There is little difference in diagnostic test accuracy between the technetium and combined tests. The combined test may reduce the number of women with 'missed' groin node metastases compared with technetium only. Blue dye alone may be associated with more 'missed' cases compared with tests using technetium. Sentinel node assessment with technetium-based tests will reduce the need for IFL by 70% in women with early vulval cancer. It is not yet clear how the survival of women with negative sentinel nodes compares to those undergoing standard surgery (IFL). A randomised controlled trial of sentinel node dissection and IFL has methodological and ethical issues, therefore more observational data on the survival of women with early vulval cancer are needed.

26P - Gene Expression of ESR1, PGR and HER2 in Lymph Node Homogenates and Concordance with IHC in Primary Breast Tumours

Aim: To determine whether extracts from the molecular assessment of sentinel lymph node (LN) status may be used (i) to assess ER, PR or HER2 status and (ii) as a resource for assessing other molecular markers in axillary LNs. Background: One-step nucleic acid amplification (OSNA) is used for rapid detection of sentinel LN metastases. Based on the RNA level of cytokeratin 19 (KRT19) an epithelial marker, in LN extracts, the LN is classified as negative, ‘+’ positive or ‘+ +’ positive. Measurement of molecular markers in these extracts could be clinically useful when insufficient invasive tissue is present in the primary to characterize these markers and may have research applications. Patients and methods: 800 consecutive LN homogenates remaining after OSNA tests yielded 39 OSNA ++ cases. Additional HER2 + (IHC 3+) and ER -ve cases were identified from 400 further LN homogenates to give a final set of 48 OSNA ‘+ +’ cases (7 HER2 +, 7 ER -ve and 9 PR -ve). 23 OSNA -ve cases were used as controls. RNA was extracted from the homogenates and gene expression of KRT19, ESR1, HER2 and PGR was assessed by QPCR. IHC data was available from routine analysis of the primary tumours. Results: As expected, KRT19 expression levels in OSNA ++ samples were much higher (mean 1840-fold) than in OSNA -ve samples. Expression levels of ESR1, HER2 and PGR were 30-40-fold higher in OSNA ++ samples compared to OSNA -ve samples. 6 of the 7 IHC HER2 + cases had the highest HER2 gene expression levels. When HER2 expression levels were normalized to KRT19 level (to account for the amount of tumour present in each LN homogenate) there was complete concordance between LN RNA and primary tumour IHC. The 7 ER -ve cases were among the 9 lowest ESR1 gene expression levels; normalization to KRT19 did not improve the association. The 9 PR -ve cases were among the 13 lowest PGR gene expression levels; normalization to KRT19 lost any concordance for PR. Conclusion: These novel data indicate that LN extracts remaining after OSNA may have clinical utility for the measurement of HER2 and possibly ER and PR status. The data also suggest that RNA extracts from LNs are a resource for understanding the molecular characteristics of those cells with the greatest potential for metastatic spread. Disclosure: All authors have declared no conflicts of interest.