Assessment Of Sentinel Lymph Nodes Research Articles

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

ObjectiveTo determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. MethodsRetrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. ResultsOne hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2–3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. ConclusionsInformation from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

246 (PB-070) Poster - One-step nucleic acid amplification assay in palpable and non-palpable breast tumours

Background: The one-step nucleic acid amplification (OSNA) assay quantifies the cytokeratin 19 (CK19) messenger RNA copy number, which is currently being used for assessment of axillary sentinel lymph node (SLN) status in breast cancer. The total tumour load (TTL), defined as the total amount of CK19 mRNA copies in all positive SLNs, may help predicting additional metastatic axillary involvement besides SLN. There is evidence suggesting that palpable and non-palpable breast tumours manifest distinct pathological features, making tumour palpability a putative predictive factor of axillary lymph node involvement.

Lymph Node and Distant Metastases in Phyllodes Tumor of the Breast.

A 54-year-old woman who incidentally noticed a "knot" in her left breast subsequently underwent excisional biopsy which yielded a diagnosis of malignant neoplasm with sarcomatous features. Given the broad differential diagnosis and imaging findings, the patient underwent bilateral mastectomy and intraoperative sentinel lymph node assessment. An 8.5 cm tumor that was further classified as a malignant phyllodes tumor was identified in the left breast, while the frozen section interpretation came back as positive for metastatic disease which resulted in left axillary lymphadenectomy. Two months later the patient progressed to distant metastatic disease and unfortunately passed away within 6 months after her initial diagnosis. Lymph node metastasis in phyllodes tumor is an exceptionally rare event for which patients usually do not undergo intraoperative sentinel lymph node examination; however high clinical suspicion of metastatic disease would be evidence for further investigation.

A clinical diagnostic test on the detection of sentinel lymph node metastasis in breast neoplasms using a 1-step RT-PCR.

Currently, assessment of sentinel lymph node (SLN) requires cytology, hematoxylin-eosin (HE), and immunohistochemistry (IHC). However, routine pathological slides still suffer from certain sampling errors and have time limitations. This study sought to investigate the sensitivity and specificity of SLN detection by reverse transcription-polymerase chain reaction (RT-PCR), which quantifies the expression of mammaglobin and cytokeratin-19 genes to determine SLN status. The RT-PCR detection of cycles threshold (CT) values has a direct relationship with the lymph node metastasis. This study prospectively collected 256 sentinel lymph nodes from 150 patients diagnosed with breast cancer between August and November 2017. In the detection of metastases in lymph nodes, molecular markers can be verified at the cell-level and tissue-level of tumor cells. In this study, IHC results were used as the gold standard for judging sentinel lymph node status. (I) According to the established cell models, as the lymph nodes in tumor cells increase, RT-PCR CT values decrease. (II) 83 lymph nodes were first collected, and the interpretation criteria for the molecular detection results were determined based on the IHC results. (III) The statistical analysis showed that the sensitivity of the RT-PCR was 80.49% and the specificity was 91.55%. The positive predictive and negative predictive values were 64.71% and 96.06%, respectively. There was no significant difference between RT-PCR detection and IHC detection (P=0.076). Statistical chi-square analysis also showed that the difference between intraoperative freezing and immunohistochemistry was statistically significant (P=0.000). There was a statistically significant difference between intraoperative freezing and RT-PCR detection (P=0.000). RT-PCR detection is more sensitive than intraoperative frozen detection, and is closer to the results of immunohistochemistry. RT-PCR had objective and rapid output advantages, and was proven to be true and reliable. RT-PCR detection can not only rapidly assess sentinel lymph node status in breast cancer patients during surgery, but its accuracy is also close to that of IHC. Correctly determine whether to perform axillary lymph node dissection and improve the survival rate of patients.

526MO Pathological assessment of sentinel lymph node in early-stage cervical cancer: Results from the prospective SENTIX trial (CEEGOG-CX01; ENGOT-CX2)

Lymph node (LN) involvement is the key factor indicating adjuvant treatment in early-stage cervical cancer patients. Both macrometastases (MAC; >2mm) and micrometastases (MIC; 0.2-2 mm) are considered LN positive (pN1) since a negative impact of MIC similar to MAC has been confirmed by several studies. Although the majority of MIC are detected only by pathological ultrastaging of LN, no international protocol for pathological assessment has been agreed upon and still sparks controversy.

Prognostic Significance of Size, Location, and Number of Lymph Node Metastases in Endometrial Carcinoma.

Regional lymph node metastasis is a well-established negative predictive prognostic factor in endometrial carcinomas. Recently, our approach to the pathologic evaluation of lymph nodes in endometrial carcinomas has changed, mainly due to the utilization of immunohistochemical stains in the assessment of sentinel lymph nodes, which may result in the identification of previously unrecognized disease [particularly isolated tumor cells (ITCs)] on hematoxylin and eosin stained slides. However, the clinical significance of this finding is not entirely clear. Following the experience in other organs systems such as breast, the Eight Edition of the American Joint Committee on Cancer's Cancer Staging Manual has recommended utilizing the N0(i+) terminology for this finding, without impact in the final tumor stage. We performed a comparative retrospective multi-institutional survival analysis of 247 patients with endometrial carcinoma with regional lymph node metastasis of various sizes identified in nonsentinel lymphadenectomy, demonstrating that the cumulative survival of patients with isolated tumor cells in regional lymph nodes is not statistically different from patient with negative lymph nodes, and is statistically different from those with lymph nodes showing micrometastasis or larger metastatic deposits. In addition, we evaluated the prognostic implications of the number of involved regional lymph nodes, demonstrating a worsening prognosis as the number of involved lymph nodes increases from none to one, and from one to more than one. Our data suggests that regional lymph nodes with isolated tumor cells in patients with endometrial carcinoma should likely be considered, for staging purposes, as negative lymph nodes, simply indicating their presence with the (i+) terminology.

Does race impact uterine cancer surgical treatment: An SGO Clinical Outcomes Registry analysis (056)

<b>Objectives:</b> The age-adjusted mortality due to endometrial cancer (EC) among Black women (BW) is approximately 84% higher than it is for White women (WW). Multiple analyses of national registry data have revealed that BW with EC are more likely to receive guideline-discordant care. The objective of this study was to determine whether BW with EC in the SGO Clinical Outcomes Registry (SGO-COR) received surgical treatment differing from that of WW. <b>Methods:</b> The SGO-COR was comprised of validated clinical data from 29 SGO-COR centers collected between 2014 and 2018. Statistical analysis was performed using student's t-test and Chi-square with Stata v.14. A p-value of <0.05 was used for statistical significance. <b>Results:</b> In this cohort of 6984 total EC patients, 4338 underwent surgical management. Of those, 287 (6.6%) were Black, and 3792 (87%) were White. There was no difference in mean BMI (36.9 vs 36; p=0.86) or prevalence of diabetes (31% vs 26%; p=0.07) between BW and WW, but BW were more likely to be ASA >class II than WW (219/274, 80% vs 1921/3593, 53.4%; p<0.00001). Additional clinical data can be found in Table 1. BW were more likely to have > stage I disease (182/287, 63% vs 2980/3792, 78.5%; p<0.0001), non-endometrioid histology (135/287, 47% vs 702/3792, 18.5%; p<0.00001) and grade 3 disease (110/287, 38.3% vs 785/3792, 20.7%, p<0.00001). WW with stage I disease were more likely to undergo minimally invasive surgery (MIS) than BW with stage I disease (2693/2930, 91.9% vs 144/172, 83.7%, p=0.00019) as well as sentinel lymph node assessment (1004/2980, 33.6% vs 29/182, 16% p<0.00001). There was no difference in conversion to laparotomy between the groups (14/254, 5.5% for BW vs 116/3594, 3.2% for WW; p=0.05). There was no statistical difference in pelvic or para-aortic lymphadenectomy regardless of stage in BW versus WW. There were no differences in gross residual disease among BW and WW (9/223, 4% vs 2.1%, p=0.07). There was no difference in the rate of postoperative complications between BW versus WW. <b>Conclusions:</b> These SGO-COR results reflect several known trends, including BW being more likely to present with more advanced, higher-grade EC and non-endometrioid histology than WW. Contrary to previous studies, BW and WW received the same surgical care in some domains (rate of lymphadenectomy, presence of residual disease, rate of complications) but were less likely to be offered an MIS approach or undergo sentinel lymph node mapping. This may reflect that the Black women with EC in this dataset already overcame a major barrier to care by obtaining access to an SGO-COR center and likely a gynecologic oncologist. The disparity in MIS and sentinel node assessment may reflect the more advanced-stage and aggressive histologies noted in BW relative to WW, but provider biases resulting in this difference should also be addressed. This study is limited by an under-representation of Black patients relative to the general US population.

Outcome of Patients with High-Risk Endometrial Cancer Undergoing Sentinel Lymph Node Assessment versus Full Lymphadenectomy (070)

Objectives: Sentinel lymph node mapping and dissection (SLN) is endorsed by the National Comprehensive Cancer Network as a recommended surgical staging approach in patients diagnosed with apparent uterine-confined endometrial cancer (EC) of all histologies. While SLN has been validated for use in patients with high-risk histologies, data regarding the oncologic safety of SLN in the management of high-risk EC is limited and inconclusive. The objective of this study was to determine the 3-year progression-free survival (PFS) and overall survival (OS) in patients with high-risk EC who underwent SLN compared to patients who underwent pelvic ± para-aortic lymphadenectomy (LND). Methods: All patients in our healthcare system diagnosed with EC with no radiologic evidence of extra-uterine disease who underwent surgical management between January 1, 2014, and September 1, 2020, were identified, and follow-up data were recorded. SLN was performed in accordance with evidence-based practice, and an SLN algorithm was used. High-risk EC was classified based on hysterectomy specimen pathology demonstrating non-endometrioid histology or FIGO grade 3 endometrioid histology. Patients were excluded if they had more than one primary cancer at the time of diagnosis or if no follow-up records were available. Patients were categorized based on intention to treat. All statistical analyses were performed using SAS version 9.4. Conclusions: Patients with high-risk EC who underwent SLN had no difference in 3-year survival relative to LND; however, the SLN group experienced shorter unadjusted OS. When adjusting for age, adjuvant therapy, and surgical approach, the two methods were found to be similar, with a trend towards worse OS for those who underwent SLN. A randomized control trial comparing SLN versus LND with long-term follow-up for patients with EC of high-risk histologies is necessary. Objectives: Sentinel lymph node mapping and dissection (SLN) is endorsed by the National Comprehensive Cancer Network as a recommended surgical staging approach in patients diagnosed with apparent uterine-confined endometrial cancer (EC) of all histologies. While SLN has been validated for use in patients with high-risk histologies, data regarding the oncologic safety of SLN in the management of high-risk EC is limited and inconclusive. The objective of this study was to determine the 3-year progression-free survival (PFS) and overall survival (OS) in patients with high-risk EC who underwent SLN compared to patients who underwent pelvic ± para-aortic lymphadenectomy (LND). Methods: All patients in our healthcare system diagnosed with EC with no radiologic evidence of extra-uterine disease who underwent surgical management between January 1, 2014, and September 1, 2020, were identified, and follow-up data were recorded. SLN was performed in accordance with evidence-based practice, and an SLN algorithm was used. High-risk EC was classified based on hysterectomy specimen pathology demonstrating non-endometrioid histology or FIGO grade 3 endometrioid histology. Patients were excluded if they had more than one primary cancer at the time of diagnosis or if no follow-up records were available. Patients were categorized based on intention to treat. All statistical analyses were performed using SAS version 9.4. Conclusions: Patients with high-risk EC who underwent SLN had no difference in 3-year survival relative to LND; however, the SLN group experienced shorter unadjusted OS. When adjusting for age, adjuvant therapy, and surgical approach, the two methods were found to be similar, with a trend towards worse OS for those who underwent SLN. A randomized control trial comparing SLN versus LND with long-term follow-up for patients with EC of high-risk histologies is necessary.

ASO Visual Abstract: Lack of Clinical Value for Immunohistochemistry for Sentinel Lymph Node Assessment in Invasive Lobular Carcinoma.

ASO Visual Abstract: Lack of Clinical Value for Immunohistochemistry for Sentinel Lymph Node Assessment in Invasive Lobular Carcinoma.

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy

ObjectivesThe goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from...

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.

Lack of Clinical Value for Immunohistochemistry for Sentinel Lymph Node Assessment in Invasive Lobular Carcinoma.

The distinct histologic appearance of invasive lobular carcinoma (ILC) may pose diagnostic challenges for sentinel lymph node (SLN) analysis. We evaluated the impact of cytokeratin immunohistochemistry (IHC) on SLN assessment in ILC and its contribution to pathologic nodal upstaging. We identified ILC patients treated with SLN surgery at our institution between September 2008 and August 2021. IHC for SLN assessment was employed at the discretion of the pathologist. Differences between groups evaluated with and without IHC were compared using Chi-square tests. Overall, 608 cases of ILC were identified in patients who underwent SLN surgery. IHC was used in 301 cases (49.5%)and was not associated with cT category, pT category, or tumor grade. Use of IHC increased detection of SLN+ disease when isolated tumor cells (ITCs) were included in the analysis (35.9% with IHC vs. 21.2% without IHC; p<0.001). There was no effect on nodal upstaging to micrometastatic disease (pN1mi) or greater (21.9% with IHC vs. 21.2% without IHC; p=0.82). IHC did not increase the number of positive SLNs detected (median 1 with and without IHC) nor did it increase axillary lymph node dissection (ALND) rates (11.6% with IHC vs. 15.3% without IHC; p=0.18). IHC improved detection of pN0(i+) disease among ILC patients undergoing SLN surgery. IHC did not increase upstaging to pN1mi or higher categories of nodal disease, detection of a greater number of positive SLNs, or ALND rates. Our data suggest routine use of IHC for SLN assessment in ILC patients does not add clinical utility.

Evaluation of Intraoperative Frozen Section Analysis with Final Histopathology Results for Sentinel Lymph Node Biopsy: Z0011 Criteria Eligible Versus Ineligible Breast Cancer Patients.

Background Intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLNs) declined in the post American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial era. However, for those patients who do not meet the ACOSOG Z0011 criteria, FSA continues to be a valuable tool in intraoperative decision-making for axillary lymph node dissection (ALND). The aim of this study was therefore to retrospectively evaluate the benefit and accuracy of FSA of Z0011 criteria eligible versus ineligible patients and identify possible predictive factors for false negative results. Methods Intraoperative FSA was performed on SLNs of 522 cT1–T3 breast cancer patients between 2008 and 2013. Clinicopathologic characteristics were retrospectively assessed by chart review. Results Overall FSA sensitivity and specificity was 67.8% and 100%. Sensitivity was generally higher for macrometastasis than for micrometastasis. The Z0011 eligible group showed a sensitivity and specificity of 72.7% and 100% versus 62.1% and 100% in the Z0011 ineligible group. Importantly, subgroup analysis of ≤ 2 versus > 2 positive SLNs of the Z0011 eligible group demonstrated both a 100% specificity and sensitivity. Several clinicopathologic factors were associated with a higher rate of false negative results in the Z0011 ineligible patient group. FSA was beneficial for 22.2% of Z0011 ineligible patients and for only 0.6% of Z0011 eligible patients regarding intraoperative decision-making for ALND. Conclusions FSA continues to be especially beneficial in the intraoperative assessment of SLNs in the Z0011 ineligible group to prevent second stage ALND. Despite an overall lower FSA sensitivity in the Z0011 eligible patient group, FSA offers in both groups a comparable high sensitivity and diagnostic accuracy for macrometastasis.

One-Step Nucleic Acid Amplification System in Comparison to the Intraoperative Frozen Section and Definitive Histological Examination Among Breast Cancer Patients: A Retrospective Survival Study.

Simple SummaryImplementing intraoperative assessment of sentinel lymph nodes by one-step nucleic acid amplification in early breast cancer can reduce the surgical burden to the patient and the costs to the health system. However, only limited data are available in terms of long-term disease-free survival and overall survival. Therefore, this study aims to compare disease-free survival and overall survival between one-step nucleic acid amplification, frozen section, and definitive histology. These results could impact the healthcare community, adding further proof to the body of evidence supporting the broader adoption of this innovative technology that enables a safe reduction in patient surgical burden and healthcare costs.BackgroundThe one-step nucleic acid amplification (OSNA) system is a novel molecular technique, which consents to quick intraoperative detection of sentinel lymph node metastases by the amplification of cytokeratin 19 mRNA. Our study aims to evaluate the OSNA method in comparison with frozen section (FS) and definitive histological examination of the sentinel lymph node biopsy among early breast cancer patients considering disease-free survival (DFS) and overall survival (OS).MethodsIn this study, we included all women who underwent sentinel lymph node biopsy (SLNB) for breast cancers classified as TNM stage I and II in our center between January 2005 and January 2017, and the follow-up was collected up to January 2019. We divided patients among three groups based on SLNB evaluation: definitive histological examination, intra-operative FS, or OSNA.ResultsWe included 2412 SLNBs: 727 by definitive histological examination, 697 by FS, and 988 by OSNA. Isolated tumor cells were found in 2.32% of cases, micrometastasis in 9.12%, and macrometastases in 13.64%. Surgical procedure duration was significantly shorter in OSNA than in FS (42.1 minutes ±5.1 vs. 70.1 minutes ±10.5, p <0.05). No significant differences have been observed among the three groups regarding OS, DSF, cumulative local, or distant metastases. In particular 5-year DFS was 96.38% in definitive histology (95% C.I. 95.02-97.75%), 96.37% in FS (95% C.I. 94.98-97.78%), and 96.51% in OSNA group (95% C.I. 95.32-97.72%).ConclusionsNo difference in OS and DFS was found comparing OSNA, FS, and definitive histology. Furthermore, reduced operative time was found in the OSNA group.

One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study

One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.

Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer.

To examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer. Retrospective cohort study. United States inpatient and outpatient hospital services. Women with endometrial cancer who underwent a laparoscopic or robotic-assisted hysterectomy. The Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost. Utilisation rates, morbidity and cost of both lymph node dissection and SLN mapping. Among 45381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23214 patients (51.2%) and no lymphatic evaluation was performed for 14399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p<0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic-assisted hysterectomy were associated with SLN mapping (p<0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR0.85, 95%CI 0.77-0.95). The median hospital costs for women who underwent SLN mapping ($10479) and lymph node dissection ($10747) were higher than for those who did not undergo nodal assessment ($9149) (p<0.001). The performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone. SLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.

Role of sentinel lymph node biopsy for gynecologic cancers.

To provide an overview of the current knowledge and recent advances of sentinel lymph node (SLN) assessment in uterine, cervical, vulvar, and ovarian cancers. In endometrial cancer, SLN evaluation has become increasingly utilized as part of the treatment of early-stage disease, with data showing improved detection of pelvic lymph node metastasis. In cervical cancer, SLN biopsy has also gained increasing traction with studies demonstrating the feasibility and accuracy of SLN detection. Evaluation with frozen section, however, remains limited in the detection of metastases. The prognostic significance of positive SLN in vulvar cancer is currently being investigated, with preliminary data showing lower recurrence rates in patients receiving adjuvant radiation. SLN evaluation remains standard of care to detect lymph node metastasis in early-staged endometrial cancer. In cervical cancer, SLN biopsy has been shown to be reliable, while decreasing morbidity without impacting disease-free survival in select patients. The technique and high sensitivity of SLN biopsy in vulvar cancer has been demonstrated in large prospective trials. There are no randomized controlled trials in ovarian cancer that evaluate the role of SLN biopsy on treatment and outcome; current SLN evaluation remains investigational.

The accuracy of intraoperative frozen section examination of sentinel lymph nodes in squamous cell cancer of the vulva

ObjectiveTo assess the diagnostic accuracy of intraoperative pathologic examination of sentinel lymph nodes (SLNs) and patient outcomes in vulva cancer. MethodsThis retrospective study included patients with unifocal, <4 cm, invasive vulvar squamous cell carcinoma and clinically negative groin nodes treated with SLN biopsy from January 2008–March 2020. Intraoperative SLN frozen section and final pathology were compared. If the SLN was negative, inguinal femoral lymphadenectomy (IFLD) was omitted. Recurrence location and groin recurrence free survival (RFS) were assessed. ResultsThe SLN cohort included 173 patients, with 258 groins. On frozen section, there were 36/258 positive and 222 negative groins. On final pathology, there were 39/258 positive: 31 macrometastases, 6 micrometastases, 2 isolated tumor cells (ITCs) and 219 negative groins. The sensitivity, specificity, PPV and NPV for intraoperative detection of metastatic disease, was 89.7% and 99.5%, 97.2% and 98.2%, respectively. There was 1 false positive and 4 false negative frozen section results where final pathology revealed 2 ITCs, 1 micrometastasis and 1 macrometastasis. Based on intraoperative results, thirty patients (17.3%) underwent immediate IFLD.Median follow up was 38.0 (1–137.8) months. The 3-year groin RFS was 91.6% (95% CI 86.2–97.4%) for negative SLNs and 64.6% (95% CI 46.5–89.7%) for positive SLNs on frozen section. Similarly, the 3-year groin RFS was 91.7% (95% CI 86.3–97.4%) for negative, 58.4% (95% CI 38.5–87.7%) for macrometastases and 100% for micrometastases/ITCs on final pathology. ConclusionsIntraoperative assessment of SLNs is accurate to determine need for IFLD and does not compromise patient outcomes in vulvar cancer.

Detection and Characterization of Sentinel Lymph Node by Ultrasound Molecular Imaging with B7-H3-Targeted Microbubbles in Orthotopic Breast Cancer Model in Mice.

Accurate identification and assessment of sentinel lymph node (SLN) using noninvasive imaging methods can play a vital role in tumor staging, surgical planning, and prognostic evaluation. In this study, we assessed the efficacy of B7-H3-targeted molecular-ultrasound imaging for the early SLN detection, and characterization in a mouse model of orthotopic breast cancer. We established a mouse breast cancer model with lymph node metastasis by injecting MAD-MB 231 cells which were engineered to express firefly luciferase reporter gene into the fat pad of the right 4th mammary gland in female BALB/c nude mice. The sole lymph node (LN) close to the tumor was regarded as the SLN for imaging investigation, which included metastatic and non-metastatic SLNs. The LN in the right 4th mammary gland from normal mice was used as normal control (normal mice LN). The commercially available preclinical streptavidin-coated, perfluorocarbon-containing lipid-shelled microbubbles (VisualSonics, Toronto, Canada) were used to generate B7-H3-targeted microbubbles (MBB7-H3) and control microbubbles (MBControl). Then, ultrasound molecular imaging (USMI) was performed using a high-resolution transducer (MS250; center frequency, 21MHz; Vevo 2100; VisualSonics, Toronto, Canada) after intravenous injection of microbubbles. The SLN was clearly detected and located under conventional (B-mode) and contrast-enhanced ultrasonography with microbubble injection. The metastatic SLNs showed a markedly higher signal from B7-H3-targeted microbubbles (MBB7-H3) compared to the non-metastatic SLNs and normal LNs. The metastatic SLN was further confirmed by ex vivo bioluminescence imaging and eventually verified by histological analysis. Our findings suggest the potential value of USMI using B7-H3 targeted microbubbles in breast cancer and establish an effective imaging method for the non-invasive detection and characterization of SLN.

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients.

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p=0.002) and high Ki-67 labeling index value (p=0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42-11.0]; p=0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.