Intraoperative Sentinel Lymph Node Biopsy Research Articles

Abstract P2-01-32: Comparison between positive and false-negative sentinel lymph nodes in breast cancer patients

Abstract Background: Intra-operative sentinel node biopsy (SNB) is performed for clinically node negative invasive carcinoma (IC). Despite a negative result for metastasis from rapid frozen section (FS) diagnosis of intra-operative SNB, some cases may be diagnosed positive when permanent sections (PS) are analyzed (i.e., false negative). In order to reduce the false-negative rate, it is necessary to determine why macrometastases measuring greater than 2 mm cannot be accurately diagnosed using frozen specimens. The aim of this study was to compare the pathological characteristics of false-negative and positive cases of macrometastasis using FSs. We also reviewed whether there were differences in postoperative prognoses between positive and false-negative cases. Methods: We retrospectively reviewed 1632 intra-operative SNBs collected from 2008 to 2011 at St. Luke’s International Hospital, Tokyo, JAPAN. Of these, 980 patients had undergone surgery for the treatment of IC without neoadjuvant chemotherapy. Lymph nodes were sectioned every 2 mm and examined. For FSs, we performed hematoxylin and eosin (HE) staining, and for PSs, we used HE and cytokeratin (AE1/AE3) staining. Image J (NIH Image, Bethesda, MD, USA) was used for assessment of the metastatic area of lymph nodes. Micro- and macrometastases were defined as metastatic lesions measuring between 0.2 and 2 mm or measuring 2 mm or more, according to TMN classification. Results: Using FSs, we identified 104 patients (10.6%) who were positive for macrometastasis, 16 patients (1.6%) who were positive for micrometastasis, and 860 patients (87.8%) who were negative for metastasis. Of the negative cases, the result was changed to micrometastasis in 37 cases (4.3%) and to macrometastasis (false-negative cases) in 14 cases (1.6%). Ten of the 14 patients did not have additional axillary lymph nodes dissection. The mean age of the patients was 55.1 ± 3.1 years for false-negative cases and 52.3 ± 1.2 years for positive cases. In terms of histological features, there were statistically significant differences between false-negative and positive cases for invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and IDC plus ILC (p < 0.05). There were no statistically significant differences between false-negative and positive cases in terms of the total number of slices for lymph nodes (8.4 ± 1.6 vs. 9.7 ± 0.6, respectively; p = 0.41) but tendency in the number of slices for metastases (2.4 ± 1.2 vs. 4.8 ± 0.5, respectively; p = 0.07). The maximum area ratio of metastasis was significantly lower in false-negative cases than in positive cases (3.0% ± 0.1% vs. 20.0% ± 0.2%, respectively; p < 0.05). There was no significant difference in disease-free survival between false-negative and positive cases (p = 0.43). Conclusions: Although it is necessary to reduce false-negative cases, no difference in prognosis was detected in our study. False-negative cases had lower metastasis area ratios than positive cases diagnosed using rapid diagnosis of intra-operative SNBs, and ILC is known to be high in histological features. Therefore, using AE1/AE3 stain together with rapid diagnosis of intra-operative SNBs may lower the false-negative rate when a diagnosis includes ILC in pre-operation analysis. Citation Format: Eriko Abe, Naoki Hayashi, Toshinao Onoda, Yang Yang, Mieko Uno, Hideko Yamauchi, Sachiko Ohde, Koyu Suzuki. Comparison between positive and false-negative sentinel lymph nodes in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-32.

Sentinel lymph node biopsy in breast cancer: the role of micrometastasis.

Intraoperative sentinel lymph node biopsy is widely used in patients with early-stage breast cancer for staging the axilla. The conventional analysis of the SLN has classically been performed by frozen section or touch imprint with a rapid H&E (hematoxylin and eosin) staining. Because of the risk of false-negative results, it has been replaced by the one-step acid amplification (OSNA) assay, a molecular diagnostic assay for the detection of cytokeratin 19 mRNA expression. Due to the controversial for the use of OSNA to evaluate the SLN because of its cost-effective and the lack of consensus to perform or avoid a lymphadenectomy when there is micrometastasis, we analyze 410 patients subjected to SLN biopsy in Hospital Puerta de Hierro, Madrid (Spain). Of the total of nodes, 223 (54.4%) were processed throughout frozen-section examination and imprint cytology and 187 (45.6%) throughout OSNA. The specificity of the frozen-section histological examination was of 100%, with a sensitivity of 83.33% (95% CI 73.07-93.60). Of the 40 patients with definitive micrometastasis in the SLN, axillary dissection was performed in 90% of the patients, with subsequent positive affectation in four of them (11.11%). Based on our result and taking into account that 10% of the lymphadenectomy performed after micrometastasis are positive, we do not believe that lymphadenectomy should be avoided after N(mi+) is detected in a SLN.

High Resolution Magic Angle Proton Magnetic Resonance Spectroscopy (HRMAS) in Intact Sentinel Node Biopsy from Breast Cancer Patients: A New Diagnostic Tool!

Introduction: The extent of axillary lymph node involvement is one of the most important prognostic markers in patients of breast cancer. However, axillary dissection is associated with significant morbidity. The intra-operative sentinel node biopsy (SNB) provides a basis for omitting the routine axillary clearance however; use of in-house frozen section histopathology is required in order to substitute later. We report the use of in vitro high resolution magic angle proton magnetic resonance spectroscopy (HRMAS) for assessing the axillary nodal status with increased sensitivity. Methods: Freshly removed axillary lymph nodes (n=17) obtained during sentinel node biopsy from 17 different patients were bisected. One segment of the bisected node was snap frozen and transported to HRMAS laboratory and was blindly subjected to 400 MHz high resolution magic angle proton magnetic resonance spectroscopy. The other portion was sent for frozen section biopsy. The tissues specimens used for HRMAS analysis and remaining portion of bisected node were then formalin fixed, paraffin embedded and sent for histo-pathological examination in separate vials. The metabolic profiles of these nodes were correlated with the routine histo-pathogical findings. Results: On histo-pathological examination, 7 nodes were found to be positive for metastasis were as 10 nodes were negative. The spectra of nodes (n=7) found to be positive for malignant cells were exclusively dominated by signals from choline, choline containing compounds and lactate in the spectral region of 3.2 ppm and 4.12 ppm respectively. Overall the sensitivity and specificity of HRMAS in the present study was 100%. Conclusion: Metastatic and non-involved lymph nodes in breast cancer can be accurately distinguished based on its metabolic profile. The technique of high resolution magic angle proton magnetic resonance spectroscopy can be utilized in enhancing the sensitivity and specificity of sentinel node biopsy and may replace frozen section histopathology

Application of nuclear medicine to achieve less invasive surgery for malignant solid tumors in children.

The use of nuclear medicine for the management of malignant tumor, such as radioguided surgery and sentinel lymph node biopsy (SLNB), has been widely accepted in the adult practice. However, there are very few studies to apply those techniques for pediatric diseases. The aim of this study was to investigate the feasibility of application of nuclear medicine in surgery for neuroblastoma (NB) or rhabdomyosarcoma (RMS) in children. Radioguided surgery using (123) I-metaiodobenzylguanidine was performed on six children with NB. SLNB using technetium-labeled tin or sulfur colloid was performed on two children with perineal RMS. Histological evaluation of resected specimens was performed to determine the accuracy of intraoperative detection and SLNB. All patients were evaluated for overall survival and complications. Intraoperative tumor localization using hand-held gamma probe was helpful in 85.7% of NB patients. Sensitivity and specificity of this technique were 81.8% and 93.3%, respectively. There were no postoperative complications, and four out of five patients with high-risk NB experienced disease-free survival (median follow up, 57 months). Sentinel lymph nodes were easily detected in patients with perineal RMS, and histological assessment revealed complete consistency with regional lymph node status. Nuclear medicine may have a potential application in the use of less invasive surgery for advanced NB or perineal RMS, the two most challenging pediatric malignancies.

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.

Triple assessment of sentinel lymph node metastasis in early breast cancer using preoperative CTLG, intraoperative fluorescence navigation and OSNA.

Sentinel lymph node biopsy (SLNB) became a standard surgical procedure for patients with early breast cancer; however, the optimal method of sentinel lymph node (SLN) identification remains controversial. The current study presents the protocol of our institution for preoperative and intraoperative SLN detection. Fifty female patients with early breast cancer and clinically node-negative axilla were enrolled in this study. All patients underwent preoperative CT lymphography (CTLG), intraoperative SLNB using fluorescence navigation, intraoperative one-step nucleic acid amplification (OSNA) and postoperative hematoxylin and eosin histopathological analysis. Prediction of metastasis by CTLG and detection of metastasis by OSNA were compared to results of histopathology as standard reference. SLN were identified by preoperative CTLG and intraoperative SLNB with fluorescence navigation in all patients, the identification rate was 100 %. SLN metastases were detected as positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I). SLN metastases were detected as positive by histopathology in 10 patients (20 %). The concordance rate between OSNA and permanent sections was 90 %. The negative predictive value of CTLG was 80 %. Use of CTLG and fluorescence navigation made performing SLNB with high accuracy possible in institutions that cannot use the radioisotope method. OSNA provided accurate intraoperative method, allowing for completion of axillary node dissection during surgery and avoidance of second surgical procedure in patients with positive SLNs, thereby reducing patient distress and, finally, saving hospital costs.

Lymph node shape in computed tomography imaging as a predictor for axillary lymph node metastasis in patients with breast cancer.

The aim of the present study was to evaluate whether preoperative computed tomography (CT) is a useful modality for the diagnosis of axillary lymph node metastasis. The axillary lymph node status was examined in patients with primary breast cancer who had undergone surgery. In total, 75 patients were analyzed with preoperative contrast CT images, following which the patients underwent an intraoperative sentinel lymph node biopsy to determine possible predictors of axillary lymph node metastasis. The lymph node shape was classified into three groups, which included fat-, clear-and obscure-types. Multivariate analysis revealed that clear-type lymph nodes in preoperative contrast CT imaging may be an independent predictor of lymph node metastasis (odds ratio, 15; P=0.003). Therefore, the results indicated that preoperative CT examination is useful to predict axillary lymph node metastasis.

Radioguided localisation of impalpable breast lesions using 99m-Technetium macroaggregated albumin: Lessons learnt during introduction of a new technique to guide preoperative localisation.

IntroductionPreoperative wire-guided localisation (WGL) of impalpable breast lesions is widely used but can be technically difficult. Risks include wire migration, inaccurate placement, and inadequate surgical margins. Research shows that radioguided occult lesion localisation (ROLL) is quicker, easier, and can improve surgical and cosmetic outcomes. An audited introduction of ROLL was conducted to validate the technique as a feasible alternative to WGL.MethodsFifty patients with single impalpable lesions and biopsy proven malignancy or indeterminate histology underwent WGL followed by intralesional radiopharmaceutical injection of 99m-Technetium macroaggregated albumin. Postprocedural mammography was performed to demonstrate wire position, and scintigraphy to evaluate radiopharmaceutical migration. Lymphoscintigraphy and intraoperative sentinel node biopsy were performed if indicated, followed by lesion localisation and excision using a gamma probe. Specimen imaging was performed, with immediate reexcision for visibly inadequate margins.ResultsAccurate localisation was achieved in 86% of patients with ROLL compared to 72% with WGL. All lesions were successfully removed, with clear margins in 71.8% of malignant lesions. Reexcision and intraoperative sentinel node localisation rates were equivalent to preaudit figures for WGL. ROLL was easy to perform and problems were infrequent. Inaccurate radiopharmaceutical placement necessitating WGL occurred in four patients. Minor radiopharmaceutical migration was common, but precluded using ROLL in only two cases.ConclusionsROLL is effective, simple, inexpensive, and easily learnt; however, preoperative confirmation of correct radiopharmaceutical placement using mammography and the gamma probe is important to help ensure successful lesion removal. Insertion of a backup hookwire is recommended during the initial introduction of ROLL.

Abstract P1-01-13: Intraoperative evaluation of sentinel lymph nodes using touch imprint cytology in patients with early-stage breast cancer: A series of 4367 procedures

Abstract Background: As the screening for breast cancer becomes common in China, an increasing number of early-stage breast cancer has been detected. For those patients, especially the ones with cliniaclly negetive lymph nodes, sentinel lymph node biopsy (SLNB) plays an important role in the assessment of the axillary status, while minimizing the mobidity of axillary lymph node dissection(ALND). Accurate intraoperative assessment of SLN metastases enables the selection of patients for ALND during the same operation. Touch imprint cytology (TIC) serves as a main intraoperative evaluation of SLNs in our institute since Feb-2005. The purpose of this study is to evaluate its clinical value. Methods: Early-stage breast cancer patients treated in our institute between Feb-2005 and Apr-2013 enrolled in this study. To avoid breast tissue contamination, all patients had an intraoperative SLNB performed before undergoing lumpectomy or mastectomy. The fresh SLNs were sectioned into 1.5-3.0mm pieces along the short axis, TIC was performed on both surfaces of each piece, its result was correlated with the histological assessments with Hematoxylin-Eosin (H&E) staining, which considered as the gold standard. Results: A total of 4,367 early-stage breast cancer patients enrolled in the study, and 14,112 SLNs were successfully harvested. Among those, 917 (21.0%) patients were confirmed to have at least one SLN positive for metastases, and 1343 (9.5%) positive SLNs were removed. Based on the final H&E report, the sensitivity, specificity and overall accuracy of TIC was 71.4%, 99.2% and 93.6%, respectively on a per patient basis, and 69.6%, 99.5% and 96.6%, respectively on a per node basis. The sensitivity for macrometastasis and micrometastasis was 74.8% and 26.5%, respectively on a per patient basis, and 78.9% and 25.2%, respectively on a per node basis. To discuss the influence of error results on the surgery procedure, we further reviewed the detail medical records of the patients enrolled in the recent 3 years. Of all the 3290 patiens treated between Jun-2010 and Apr-2013, 207(6.5%) patients needed a second opereation to have the ALN dissected. Meanwhile, 20(0.6%) patients had undergone extra ALND because of the false positive results of TIC. Conclusion: The sensitivity of TIC seems a little lower then the ones reported previously, but the overall accuracy still remains acceptable. In addition, only 7.1% patients were influenced by the error results of TIC, along with the advantages, such as the shorter preparation time and the less cost of cytological specimens, we consider TIC a feasible method, and believe it can serve well in the intraoperative evaluation of SLNs for early-stage breast cancer patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-13.

Intraoperative sentinel node biopsy by one-step nucleic acid amplification (OSNA) avoids axillary lymphadenectomy in women with breast cancer treated with neoadjuvant chemotherapy

There is no evidence that supports the recommendation of sentinel lymph node biopsy (SLNB) in patients with breast cancer who have treated with neoadjuvant chemotherapy (NAC) to downsize tumors in order to allow breast conservation surgery, because NAC induces anatomical alterations of the lymphatic drainage. We evaluated the effectiveness of SLNB using intraoperative one-step nucleic acid amplification (OSNA) method to detect microscopic metastases or isolated tumor cells after NAC in patients with clinically negative axillary nodes at initial presentation. We evaluated in patients with breast cancer and clinically negative axilla at presentation, the effectiveness of SLNB by OSNA after NAC (71 patients) or prior to NAC (40 patients). The rate of SLN identification was 100% in both groups. 17 women with SLNB prior to systemic treatment showed positive nodes (14 macrometastases and 3 micrometastases), and positive SLNB were detected in 15 women with SLNB after NAC, which were 14 macrometastases and 1 micrometastase. The negative predictive value of ultrasonography was 57.5% in patients with SLNB prior to neoadjuvant therapy and 78.9% in patients with chemotherapy followed by SLNB. Intraoperative SLNB using OSNA in women with clinically negative axillary lymph nodes at initial presentation who received NAC could predict axillary status with high accuracy. Also it allows us to take decisions about the indication or not to perform an axillary dissection at the moment, thus avoiding delay in the administration of chemotherapy and benefiting the patients from a single surgical procedure.

Accuracy of Frozen Section Analysis of Sentinel Lymph Nodes for the Detection of Asian Breast Cancer Micrometastasis - Experience from Pakistan

Intraoperative sentinel lymph node biopsy has now become the standard of care for patients with clinically node negative breast cancer for diagnosis and also in order to determine the need for immediate axillary clearance. Several large scale studies confirmed the diagnostic reliability of this method. However, micrometastases are frequently missed on frozen sections. Recent studies showed that both disease free interval and overall survival are significantly affected by the presence of micrometastatic disease. The aim of this study was to determine the sensitivity and specificity of intraoperative frozen section analysis of sentinel lymph nodes (SLNs) for the detection of breast cancer micrometastasis and to evaluate the status of non-sentinel lymph nodes (non-SLNs) in those patients subjected to further axillary sampling. We performed a retrospective study on 154 patients who underwent SLN biopsy from January 2008 till October 2011. The SLNs were sectioned at 2 mm intervals and submitted entirely for frozen sections. Three levels of each section submitted are examined and the results were compared with further levels on paraffin sections. Overall 40% of patients (62/154) were found to be SLN positive on final (paraffin section) histology, out of which 44 demonstrated macrometastases (>2mm) and 18 micrometastases (<2mm). The overall sensitivity and specificity of frozen section analysis of SLN for the detection of macrometastasis was found to be 100% while those for micrometastasis were 33.3% and 100%, respectively. Moreover 20% of patients who had micrometastases in SLN had positive non-SLNs on final histology. Frozen section analysis of SLNs lacks sufficient accuracy to rule out micrometastasis by current protocols. Therefore these need to be revised in order to pick up micrometastasis which appears to have clinical significance. We suggest that this can be achieved by examining more step sections of blocks.

Abstract 5287: High accuracy of microRNAs expression in the detection of lymph node metastasis in patients with oral squamous cell carcinomas.

Abstract The presence of metastatic disease in cervical lymph nodes of oral squamous cell carcinoma (OSCC) patients is one of the most important determinants in therapy choice and prognosis. Thus, the correct staging of regional lymph node metastases is critical to the success of loco-regional control of the disease, response to treatment and thus influences the overall survival of these patients. Routine clinical staging is not always efficient as it might miss occult metastasis and the post-surgical pathologic evaluation of resected lymph nodes through H&amp;E is not sensitive in detecting small metastatic deposits. Thus, there is an urgent need for diagnostic markers and techniques for a rapid and accurate detection of metastatic cells in cervical lymph nodes to guide clinicians in the choice of the most appropriate therapy for these patients. MicroRNAs are promising candidates for diagnostic markers since: (1) they play a role in many pathways involved in tumor metastasis; (2) they are reported to have tumor and tissue-specific expression; (3) their expression is evaluated using the sensitive and rapid qRT-PCR technique; (4) they are suitable to be evaluated in paraffin embedded tissue. Thus, we report here the evaluation of microRNAs as markers in detecting metastatic cells in lymph nodes from OSCC patients. An initial screening using PCR-array compared the expression of 664 microRNAs between metastatic and non-metastatic lymph nodes from 6 OSCC patients and after several inclusion and exclusion criteria, 25 microRNAs were selected as differentially expressed. Four microRNAs were selected for further validation using qRT-PCR in lymph nodes from 48 patients (23 non-metastatic, 18 with macrometastasis, 5 with micrometastasis and 2 with isolated tumor cells). All microRNAs showed 100% specificity. Two microRNAs had high levels of sensitivity (76% and 88%), but were not successful in detecting small metastatic deposits (28.6% and 57.1%). On the other hand, the other two markers were sensitive enough to detect all metastatic samples showing accuracy level, negative and positive predictive values of 100%, as well as AUC values of 1.0. These results show the feasibility of microRNAs as diagnostic markers of cervical metastasis in OSCC patients that can potentially be evaluated using several approaches at different time-points such as pre-treatment diagnostic using fine-needle aspiration biopsies, intraoperative sentinel node biopsy and after surgery as an auxiliary tool to pathology examination, immensely helping in the choice of management of these patients from initial treatment to adjuvant therapy. Citation Format: Ana Carolina de Carvalho, Danielle C. C. Maia, Andre L. Carvalho, Cristovam Scapulatempo-Neto, Andre L. Vettore. High accuracy of microRNAs expression in the detection of lymph node metastasis in patients with oral squamous cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5287. doi:10.1158/1538-7445.AM2013-5287

99mTc-tilmanocept for lymphoscintigraphy

Vital blue dyes and radiolabeled colloids are widely used globally for intraoperative lymphatic mapping and sentinel lymph node biopsy. Until very recently, however, no radiolabeled agents were specifically approved for lymphoscintigraphy and none have been tested in prospective clinical trials. 99mTc-tilmanocept was designed for use in lymphoscintigraphy and sentinel node biopsy, and has been evaluated in Phase II and Phase III clinical trials. In nonrandomized, prospective comparisons with vital blue dye, 99mTc-tilmanocept reproducibly localized in regional lymph nodes after injection at the site of primary breast carcinomas and melanomas undergoing sentinel node biopsy, detecting nearly all visibly blue nodes and identifying more tumor-containing nodes overall, without missing any blue tumor-containing nodes. A Phase III trial in head and neck squamous cell carcinomas, with all patients undergoing complete node dissection after removal of the nodes detected with 99mTc-tilmanocept, is currently underway...

Fine-Needle Aspirates CYFRA 21-1 is a Useful Tumor Marker for Detecting Axillary Lymph Node Metastasis in Breast Cancer Patients

IntroductionTo assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN) metastasis in breast cancer patients.MethodsUS-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17–92 years). Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB), and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts.ResultsAmong the 156 LNs, 75 (48.1%) were benign, and 81 (51.9%) were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001). US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05). All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001). Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076).ConclusionMeasuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients.

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

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

The usefulness and accuracy of sentinel lymph node biopsy using single photon emission computed tomography/computed tomography with 99mTc phytate to detect locoregional lymph node metastases in patients with papillary thyroid carcinoma

PurposeRegional lymph node (LN) metastases are detected in 57-85% of patients with papillary thyroid carcinoma (PTC) and are associated with increased tumor recurrence. However, the management of lymphatic disease in patients with PTC has been ongoing source of debate. We have prospectively assessed the usefulness and accuracy of sentinel LN (SLN) biopsy for the detection of LN metastases in patients with PTC on preoperative imaging using single photon emission computed tomography/computed tomography (SPECT/CT) and 99mTc phytate.MethodsWe prospectively assessed 39 patients with PTC who had risk factors for recurrence or with the necessity of intraoperative LN sampling for suspicious LN metastases on preoperative imaging from August 2010 to March 2011. The patients underwent preoperative lymphoscintigraphy and SPETC/CT and intraoperative SLN biopsy (SLNB).Results99mTc lymphoscintigraphy and SPECT/CT localized SLN in 38 patients (97.4%), with the gamma probe identifying 2.15 mean SLNs in the lateral neck of the 39 patients. Skip metastasis was found in one patient, and lateral compartment LN metastasis in 17 (43.5%). The sensitivity, specificity, and accuracy of SLNB for lateral compartment LN metastasis were 88.2%, 100%, and 94.8%, respectively. SLNB was more accurate and useful for lateral than for central compartment LN metastasis.ConclusionSPECT/CT improved SLN detection and anatomical localization compared with lymphoscintigraphy. SLNB in patients with risk factors for recurrence or the necessity of intraoperative LN sampling for suspected LN metastases on preoperative imaging was accurate in detecting LN metastases and may help in deciding whether to perform lateral compartment dissection in patients with PTC.

Sentinel lymph node biopsy using carbon nanoparticles for Chinese patients with papillary thyroid microcarcinoma

AimsTo compare the efficacies of methylene blue (MB) and carbon nanoparticles (CNs) as tracers for sentinel lymph node biopsy (SLNB), and assess the value of SLNB in predicting the cervical LN status of patients with thyroid microcarcinoma. MethodsThis retrospective analysis comprised 200 thyroid microcarcinoma patients who underwent intraoperative SLNB. Among them, 100 patients were injected with MB dye. The other 100 patients received a CN suspension injection. Routine pathological examination was performed in all resected specimens. ResultsSLNs detected in the experimental and control groups were 126 and 102, respectively, of which the metastatic LNs confirmed by histopathology were 77 and 48, respectively. The staining rate of cervical level VI LNs in the experimental group was significantly higher than that in the control group (P<0.001). For the CN method, the sensitivity, specificity, accuracy rate, and false negative rate were 93.3%, 100%, 97%, and 5.2%, respectively, whereas the corresponding figures for the MB method were 80.6%, 100%, 93%, and 9.9%, respectively. The positive rate of cancer metastases for SLNs in the experimental group was 61.1%, which is significantly higher than that in the control group (47.1%; P=0.034). ConclusionsIn contrast to the MB method, CNs can maintain the durability of SLN imaging and accurately forecast the LN status of patients with thyroid microcarcinoma; in addition, the CN method was found to be feasible and repeatable. The CN method better aids the screening and selection of patients who are most likely to benefit from cervical LN dissection.

Lysophosphatidic Acid Induces Lymphangiogenesis and IL-8 Production in Vitro in Human Lymphatic Endothelial Cells

The bioactive phospholipid lysophosphatidic acid (LPA) and its receptors LPA(1-3) are aberrantly expressed in many types of human cancer. LPA has been reported to induce tumor cell proliferation, migration, and cytokine production. However, whether LPA exerts an effect on lymphatic endothelial cells (LECs) or on lymphangiogenesis, a process of new lymphatic vessel formation that is associated with increased metastasis and poor prognosis in cancer patients, has been unknown. Here, we show that LPA induces cell proliferation, survival, migration, and tube formation, and promotes lymphangiogenesis in vitro in human dermal LECs. In addition, LPA induces IL-8 expression by enhancing IL-8 promoter activity via activation of the NF-κB pathway in LECs. Using IL-8 siRNA and IL-8 neutralizing antibody, we revealed that IL-8 plays an important role in LPA-induced lymphangiogenesis in vitro. Moreover, using siRNA inhibition, we discovered that LPA-induced lymphangiogenesis in vitro and IL-8 production are mediated via the LPA(2) receptor in LECs. Finally, using human sentinel afferent lymphatic vessel explants, we demonstrated that LPA up-regulates IL-8 production in the LECs of lymphatic endothelia. These studies provide the first evidence that LPA promotes lymphangiogenesis and induces IL-8 production in LECs; we also reveal a possible new role of LPA in the promotion of tumor progression, as well as metastasis, in different cancer types.

168 Usefulness of a New Thin-plastic-adhesive-film Method for Pathological Examination of Intraoperative Sentinel Node Biopsy

168 Usefulness of a New Thin-plastic-adhesive-film Method for Pathological Examination of Intraoperative Sentinel Node Biopsy

Is the benefit of intraoperative sentinel lymph node biopsy (SLNB) analysis using one-step nucleic-acid amplification (OSNA) negated by the need for further breast surgery?

Is the benefit of intraoperative sentinel lymph node biopsy (SLNB) analysis using one-step nucleic-acid amplification (OSNA) negated by the need for further breast surgery?