Diagnosis Of Sentinel Lymph Node Metastasis Research Articles

Long non-coding RNAs lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 present as regulators of sentinel lymph node metastasis in breast cancer.

Long non-coding RNAs (lncRNAs) participate in various biological processed involved in tumorigenesis, metastasis and proliferation. The aim of the present study was to identify candidate long non-coding RNAs (lncRNAs) involved in sentinel lymph node (SLN) metastasis in breast cancer. Specimens of SLNs were collected from patients with SLN metastasis via punch biopsy. Total RNA was extracted and RNA sequencing (RNA-seq) was conducted. Differential expression profiles of mRNAs and lncRNAs were obtained via bioinformatics analysis, and Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on differentially expressed mRNAs. The expression levels of lncRNAs were analyzed via reverse transcription-quantitative PCR (RT-qPCR), and the regulation network of the lncRNAs to downstream microRNAs (miRs) and mRNAs was predicted. Based on RNA-seq results, six differentially expressed candidate lncRNAs were identified in patients with and without SLN metastasis: lnc-ANGPTL1-3:3, lnc-GJA10-12:1, lnc-ACAN-2:1, lnc-ZPBP2-4:1, lnc-GATA3-16:1 and lnc-ACOX3-5:1. KEGG and GO analysis identified that the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways were the most enriched pathways. After RT-qPCR analysis, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 exhibited expression patterns that were consistent with those from RNA-seq. Moreover, receiver operating characteristic curve analysis demonstrated that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 expression levels had high sensitivity and specificity in the diagnosis of SLN metastasis, and that their expression levels were upregulated in patients with axillary lymph node metastasis. Further analysis revealed that lnc-GJA10-12:1 and lnc-ANGPTL1-3:3 were commonly involved in regulating the miR-302 family, including miR-302d-3p and miR-302c-3p, which together targeted AKT1. Additionally, lnc-ANGPTL1-3:3 was predicted to target miR-520b to regulate MAP3K2 expression. lnc-GJA10-12:1 was also predicted to target miR-34a-5p to regulate MAP2K1 and MAP3K9 expression levels, as well as miR-449a to regulate MAP2K1 expression. The results of the present study suggested that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 may potentially serve a role in SLN metastasis of breast cancer by regulating the PI3K/Akt and MAPK signaling pathways via targeting the miR-302 family, miR-520a-3p, miR-34a-5p and miR-449a. Thus, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 in SLN may serve as potential markers of breast cancer metastasis.

Ultrasonography-guided wire-localization and nano-carbon staining for detection of sentinel lymph node in breast cancer

Objective To evaluate the usage of ultrasound guided wire-localization, nano-carbon staining and the combination of the above two methods in detecting sentinel lymph node (SLN) in breast cancer. Methods A total of 159 cases of breast cancer from May 2015 to December 2017 in Shanxi Provincial Cancer Hospital were selected, and they were treated with ultrasound guided wire-localization, nano-carbon staining and combination of the two methods separately to detect SLN before the operation. After the operation, SLN and axillary lymph node in each group were marked and made pathological diagnosis. Results There were 69 cases with pathological diagnosis of SLN metastasis and 90 cases without abnormal representation. With the patient as the unit, the sensitivity of ultrasound guided wire-localization was 100.0% (69/69), the sensitivity of nano-carbon staining was 98.6% (68/69), and the sensitivity of combination of the two methods was 97.1% (67/69). The specificity of ultrasound guided wire-localization was 3.3% (3/90), the specificity of nano-carbon staining was 2.2% (2/90), and the specificity of combination of the two methods was 5.6% (5/90). With the count of SLN as the unit, the combination of the two methods had the highest diagnostic efficiency in detecting SLN, and the difference was statistical significant (χ2 = 34.31, P < 0.001). Conclusions Ultrasound guided wire-localization and nano-carbon staining are safe and accessible methods for detecting SLN. It provides a precise treatment for early breast cancer, and it can protect medical staff from radiation, which is expected to be the best method for detection of SLN in breast cancer. Key words: Breast neoplasms; Sentinel lymph node; Ultrasound guided wire-localization; Nano-carbon staining

SPIO-enhanced MR imaging at 3T for accurate diagnosis of sentinel node metastases to avoid sentinel node biopsy in patients with breast cancer.

68 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging at 1.5T for the detection of metastases in sentinel nodes identified by computed tomography lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol 2011, ASCO 2012). The aim of this study was to evaluate whether SPIO-enhanced MR imaging at 3T improved the diagnostic accuracy for the detection of metastases in sentinel nodes. Moreover, these results were compared with those of the diagnosis using CT-LG according to the size criteria. Methods: Seventy patients with breast cancer and clinically negative nodes were included. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging at 3T. Sentinel node size was measured on CT-LG and a node larger than 5 mm in short axis diameter was considered metastatic. Sentinel nodes localized by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 55 years (range, 29-78). Sentinel nodes were identified by CT-LG successfully in 69 (98.6%) of 70 patients. The mean number of sentinel nodes identified by CT-LG was 1.4 (range, 1-3). All 19 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Forty-eight of 50 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on the imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 100%, 96.0%, and 97.1%, respectively, on a patient-by-patient basis. Those of CT-LG were 78.9%, 56.0%, 62.3%, respectively. The specificity and accuracy of MR imaging were superior to those of CT-LG (McNemar test; p &lt; .0001 and = .0015, respectively). Conclusions: SPIO-enhanced MR imaging at 3T can accurately diagnose the sentinel node metastases, and therefore sentinel node biopsy may not be required for most patients with breast cancer.

OSNA for detection of sentinel lymph node metastasis.

74 Background: SLN (sentinel lymph node) biopsy is a common procedure in surgical treatment of clinically node-negative breast cancer. OSNA (One-step nucleic acid amplification) is a semi-automated examination using molecular biological technique, and OSNA allows straightforward diagnosis of SLN metastasis without a pathologist by quantitative evaluation of CK19 m-RNA. The objective of this study was to confirm the reliability of OSNA for detection of sentinel Lymph node metastasis, and OSNA is also useful even in neoadjuvant chemotherapy (NAC) patients. Methods: Surgically obtained 159 SLNs from 106 breast cancer patients were evaluated and compared. The SLNs were sectioned into three pieces along the major axis. The central piece was sent to pathologists in an outside laboratory for postoperative histological investigation to diagnose metastasis. The other two pieces were examined with the OSNA to detecting metastasis during an operation. The OSNA analysis and the histological investigation were compared. Then, the patients were divided into two groups, one group was the patients with NAC (22 SLNs from 13 patients), and another group was the patients without NAC (137 SLNs from 93 patients). It was examined whether those concordance rates were similar. Results: 151 SLNs were same diagnosis using both methods. 4 SLNs were negative on OSNA but positive on histology, and these 4 SLNs contained only micrometastasis lesion. Other 4 SLNs were positive on OSNA but negative on histology. The concordance rate was 95.0%. In the patients with NAC, 20 SLNs were same diagnosis. Two SLNs were negative on OSNA but positive on histology, and these 2 SLNs were micrometastasis. The concordance rate was 90.9%. In the patients without NAC, 131 SLNs were same diagnosis. 2 SLNs were positive on OSNA but negative on history, and these 2 SLNs were micrometastasis. 4 SLNs were positive on OSNA but negative on history. The concordance rate was 95.6%. Conclusions: The concordance rate in patients with NAC was as high level as the rate in patients without NAC. The false negative SLNs were all micrometastasis. These results suggest that OSNA is very useful for detecting SLN metastasis and it is clinically acceptable in NAC patients.

SPIO-enhanced MR imaging at 3T for the detection of metastases in sentinel nodes in patients with breast cancer.

1107 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging at 1.5T for the detection of metastases in sentinel nodes localized by computed tomography lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol 2011, ASCO 2012). The aim of this study was to evaluate the accuracy of MR imaging at 3T with SPIO enhancement for the detection of metastases in sentinel nodes. Methods: This study included 60 patients with breast cancer and clinically negative nodes. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging at 3T. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel nodes located by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 54.2 years (range, 33-78). Sentinel nodes were identified by CT-LG successfully in 59 (98.3%) of 60 patients. The mean number of sentinel nodes identified by CT-LG was 1.43 (range, 1-3). All 16 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Five (31.3%) of them had micrometastases. Forty-one of 43 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 100%, 95.3%, and 96.6%, respectively. No adverse events were associated with either CT or MR imaging. Conclusions: SPIO-enhanced MR imaging at 3T is useful for accurate diagnosis of sentinel node metastases, and therefore sentinel node biopsy may be avoided for most patients with breast cancer.

Determination of the Accuracy of Imprint Cytology for Intraoperative Diagnosis of Sentinel Node Metastases in Breast Cancer: A Surrogate Procedure to Frozen Section?

Determination of the Accuracy of Imprint Cytology for Intraoperative Diagnosis of Sentinel Node Metastases in Breast Cancer: A Surrogate Procedure to Frozen Section?

Abstract P1-01-27: Novel diagnostic procedure of metastasis to the sentinel lymph node of breast cancer using a semi-dry dot-blot method

Abstract Background: Sentinel lymph node (SLN) biopsy is a common surgical procedure. However, novel diagnostic modalities are required because of a shortage of pathology specialists in Japan and discordance between the intraoperative and final pathological diagnosis of SLN metastasis. Efficient methods that use molecular markers for detecting SLN metastasis, such as one-step nucleic acid amplification, are commercially available, but special equipment (e.g., thermal cycler) is costly and the problem of false-negatives for CK19 non-expressing cells remains unresolved. Recently, we developed an easy, quick and cost-effective method for detection of cancer cells in lymph nodes by applying dot-blot analysis technology, called the “semi-dry dot-blot method (SDB method)”. The SDB method visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody (AE1/AE3) and chromogen on a dot-blot membrane. This method can detect 0.01 mg/mL protein extracted from cancer tissue and 20 suspension cells (MCF-7) in approximately 20 minutes. The current study evaluated the efficacy of our SDB method in the diagnosis of SLN metastasis in breast cancer. Methods: (I) One hundred eighty dissected lymph nodes from 29 cases, including breast, lung, gastric and colorectal cancer, were analyzed. Each lymph node was sliced at the maximum diameter and washed by phosphate-buffered saline (PBS), and this lavage fluid (PBS) was used for diagnosis of LN metastasis by the SDB method, and washed lymph node was sent to pathological section for pathological diagnosis. The sensitivity, specificity and accuracy of the SDB method were determined to compare with the final pathology report. (II) A multicenter prospective clinical trial was conducted, where 132 SLN samples from 78 cases of clinically node-negative breast cancer were analyzed. Each SLN was sliced at 2-mm intervals and washed by PBS. Lavage fluid of sliced SLNs was used for the diagnosis of SLN metastasis by the SDB method in a blinded manner. The sensitivity, specificity, accuracy and the time required for the SDB method were determined and compared with the intra-operative pathology report. Results: (I) Lymph node metastasis was detected in 35 lymph nodes (19.4%). Comparison of the results between the final pathology and the SDB method showed complete concordance (accuracy: 100%). (II) Of the 132 lymph nodes eligible for analysis, 13 (10.0%) were assessed as positive and 114 as negative by the SDB method and intra-operative pathological examination, with an accuracy of 96.2%. All pathologically positive nodes, which included one micro metastasis, were also detected by the SDB method; (sensitivity: 100%). One hundred fourteen of the 119 pathologically negative nodes were assessed as negative with the SDB method (specificity: 95.8%). The mean required times of 16 cases for intra-operative pathological diagnosis and simultaneous SDB method were 43.5 and 42.2 minutes, respectively. Conclusions: The SDB method is simple, fast, accurate and cost-effective for the intra-operative diagnosis of SLN metastasis. Because there is no loss of lymph node tissue, the SDB method and pathological investigation can be performed simultaneously. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-27.

SPIO-enhanced MR imaging for axillary staging to avoid sentinel node biopsy in patients with breast cancer.

1103 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging for the detection of metastases in sentinel nodes localized by computed tomography (CT) lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol, 2011). These techniques have evolved and we report our most recent results of axillary staging using them. Methods: Previously unreported 87 consecutive patients with breast cancer and clinically negative nodes were enrolled in this study. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel nodes located by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 54.9 years (range, 34-77). Sentinel nodes were identified by CT-LG and removed successfully in all patients. The mean number of sentinel nodes identified by CT-LG was 1.16 (range, 1-2). Twenty of 22 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Fifty-eight of 65 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 91%, 89%, and 90%, respectively. Two patients whose metastases were not detected had micrometastases. No adverse events were associated with either CT or MR imaging. Conclusions: SPIO-enhanced MR imaging provided accurate axillary staging, and therefore sentinel node biopsy may not be necessary for most patients with breast cancer.

Rapid detection of sentinel lymph node metastases in different techniques and comparison in low-grade breast carcinomas

Introduction: The role of sentinel node biopsy has revolutionized breast cancer treatment. This determination reduces the mobility of a complete axillary lymphadenectomy. The aim of our study is to analyze the value of sentinel node in low-grade histological breast tumors, studied with hematoxylin and eosin techniques, Immunohistochemistry, and molecular chain reaction in real-time quantitative polymerase (RT-PCR). Materials and methods: In a pilot study we studied a total of 21 patients with histological diagnosis of mucinous carcinoma, adenoid cystic carcinoma, and medullar carcinoma that underwent the sentinel node technique. Once the lymph node was removed, it was sent to pathology, where it was fragmented and evaluated, using between 25% and 50% of the lymph node for molecular biology laboratory studies. Results: The sentinel nodes studied were 32, corresponding to the 21 patients. Of the 32 lymph nodes analyzed, 29 (90.6%) were negative on histopathological examination and the molecular identification, 2 (6.2%) were positive in both techniques and 1 (3.125%) lymph node was positive with quantitative RT-PCR and negative in histology (H&amp;E), which – subsequently by immunohistochemistry (IHC) – was diagnosed as isolated tumor cells (ITC). Conclusion: When comparing the techniques of hematoxylin and eosin, immunohistochemistry, and molecular RT-PCR technique, we found greater sensitivity of molecular techniques; this can reduce the false negative and improve diagnosis of sentinel node metastases. Patients with low histological grade carcinomas have high survival rates, less aggressive tumor behavior, and reduced lymph node at diagnosis.

P3-07-46: Accuracy of SPIO-Enhanced MR Imaging Alone for the Diagnosis of Sentinel Node Metastases in Patients with Breast Cancer.

Abstract Background Superparamagnetic iron oxide (SPIO)-enhanced MR imaging has been reported to be promising for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer (Motomura, Ann Surg Oncol 2011). The current SPIO technique involves imaging before and after contrast administration. This study evaluated the accuracy of SPIO-enhanced MR imaging alone without unenhanced imaging. Methods: This study included 120 patients with breast cancer demonstrating clinically negative nodes. Sentinel nodes were identified by CT lymphography, and MR imaging of the axilla before and 18–24 hr after interstitial administration of SPIO was performed. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if there was an absence of low signal intensity either in the entire node or in a focal area on SPIO-enhanced MR imaging. The diagnostic accuracy of the SPIO-enhanced imaging alone was compared with that of combined unenhanced and SPIO-enhanced imaging. Results: The mean number of sentinel nodes identified by CT lymphography was 1.2 (range 1–3). Pathologic evaluation demonstrated that 28 (23.3%) of 120 patients showed metastasis to at least one node. One false negative result was added when the evaluation was based solely on SPIO-enhanced MR imaging. Consequently, the sensitivity decreased from 84.0% to 80.0% and the accuracy decreased from 89.2% to 88.3%, respectively, in the SPIO-enhanced MR imaging alone. However, the differences in sensitivity and accuracy between SPIO-enhanced MR imaging alone and the combined unenhanced and SPIO-enhanced imaging were not significant (McNemar's test; p=1.0). The specificity of enhanced imaging alone and that of combined unenhanced and SPIO-enhanced imaging were both 90.5%. Conclusions: A single MR imaging examination performed after SPIO administration can be used for accurate diagnosis of sentinel node metastases, and thus reduce the time and cost of imaging. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-46.

SPIO-Enhanced Magnetic Resonance Imaging for the Detection of Metastases in Sentinel Nodes Localized by Computed Tomography Lymphography in Patients with Breast Cancer

Superparamagnetic nanoparticle-enhanced magnetic resonance (MR) imaging has been reported to be a promising improvement for diagnostic imaging of lymph node metastases from various tumors. Moreover, sentinel nodes have been reported to be well identified using computed tomography (CT) lymphography (CT-LG) in patients with breast cancer. The aim of this study was to evaluate MR imaging with superparamagnetic iron oxide (SPIO) enhancement for the detection of metastases in sentinel nodes localized by CT-LG in patients with breast cancer. This study included 102 patients with breast cancer and clinically negative nodes. Sentinel nodes were identified by CT-LG, and SPIO-enhanced MR imaging of the axilla was performed to detect metastases in the sentinel nodes. A node was considered nonmetastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show low signal intensity on MR imaging. Sentinel node biopsy was performed, and imaging results were correlated with histopathologic findings. The mean number of sentinel nodes identified by CT-LG was 1.1 (range, 1-3). The sensitivity, specificity, and accuracy of MR imaging for the diagnosis of sentinel node metastases were 84.0%, 90.9%, and 89.2%, respectively. In 4 of 10 patients with micrometastases, metastases were not detected, but all 15 patients with macrometastases were successfully identified. SPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT-LG in patients with breast cancer and may avoid sentinel node biopsy when the sentinel node is diagnosed as disease-free.

Accuracy of Intraoperative Macroscopic Diagnosis of Sentinel Node Metastases in Breast Cancer: Is Accurate Prediction Possible?

Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients who require axillary lymph node dissection, thus avoiding an additional operation. In this study we investigated the accuracy of intraoperative macroscopic diagnosis of SLN metastases in patients with breast cancer. SLNs from 276 breast cancer patients with clinically negative nodes were analyzed by macroscopic examination. The results of intraoperative macroscopic diagnosis were compared with those of frozen section analysis. The sensitivity, specificity, overall accuracy, and false negative rate of SLN biopsy in the assessment of node status were 82.1%, 100%, 96.4%, and 17.9%, respectively, for frozen section analysis, and 57.1%, 95.5%, 87.7%, and 42.9%, respectively, for macroscopic evaluation. Even in patients with node metastasis >7 mm, the false negative rate of macroscopic evaluation was 11.1%. Our results suggest that macroscopic diagnosis is less effective in predicting lymph node status in breast cancer than frozen section analysis. These findings imply that intraoperative macroscopic evaluation of sentinel nodes is never predictive of the final pathology.

Abstract P1-01-07: Touch Imprint Cytology for Intraoperative Evaluation of Sentinel Lymph Node in Patients with Early-Stage Breast Cancer: A Five-Year Experience

Abstract Background: Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissection during the same operation and reduces the need for re-operation. Touch imprint cytology (TIC) serves as a main intraoperative assessment of SLNs in our institute for over five years. The purpose of the present study is to evaluate the clinical value of TIC as an intraoperative assessment for the diagnosis of SLN. Methods: Patients treated for early-stage breast cancer between Feb-2005 and May-2010 enrolled in the study. TIC was routinely performed intraoperatively, the result of which was correlated with definitive histological assessments of serial section with Hematoxylin-Eosin staining. Subsequent immunohistochemistry staining with CK-19 and MUC-1 were performed for research purposes. The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram was applied in this retrospective study to estimate probability of SLN involvement of each case. Results: A total of 1,077 patients with early-stage breast cancer enrolled in the study, and 3,048 SLNs were successfully harvested during the surgeries. Among those, 265 (24.6%) patients proved to have at least one SLN that was positive for carcinoma. Altogether, 397 (13.0%) involved nodes were removed from patients in the aforementioned patient pool. Based on the final pathology report, the sensitivity, specificity and overall accuracy of TIC was 83.4%, 99.0% and 95.2%, respectively on a per patient basis, and 78.3%, 99.4% and 96.7%, respectively on a per node basis. The sensitivity for macrometastasis and micrometastasis are 88.6% and 39.3%, respectively on a per patient basis, while 87.4% and 31. 3%, respectively on a per node basis. Of the patients included in this study, 98.7% had a positive SLN within their first three harvested SLNs. All the patients who were at a &amp;lt;10% chance of SLNs metastases according to the MSKCC nomogram were proved to be node negative by the final pathology. Conclusion: TIC is feasible and is able to detect macrometastasis in SLNs with an acceptable accuracy for clinical use in early-stage breast cancer patients while its ability to detect micrometastasis is limited. Limiting intraoperative TIC to the first three harvested SLNs in the diagnosis of SLN metastasis may make this diagnostic procedure significantly cheaper and easier for pathologists to perform. The MSKCC nomogram could be applied as a screening tool. Intraoperative assessment for SLNs, such as TIC, could be spared for patients with extremely low MSKCC scores (&amp;lt;10%). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-07.

Optical scanning for rapid intraoperative diagnosis of sentinel node metastases in breast cancer

Intraoperative diagnosis of sentinel node metastases enables an immediate decision to proceed to axillary lymph node dissection, avoiding a second operation in node-positive women with breast cancer. An optical scanner was developed that interrogated the cut surface of bivalved, but otherwise unprocessed, sentinel lymph nodes with pulses of white light by elastic scattering spectroscopy (ESS). The scattered light underwent spectral analysis, and individual spectra were initially correlated with conventional histology to develop a diagnostic algorithm. This algorithm was used to create false colour-coded maps of scans from an independent set of nodes, and the optimal criteria for discriminating between normal and cancer spectra were defined statistically. The discriminant algorithm was developed from a training set of 2989 spectra obtained from 30 metastatic and 331 normal nodes. Subsequent scans from 129 independent nodes were analysed. The scanner detected macrometastases (larger than 2 mm) with a sensitivity of 76 per cent (69 per cent including micrometastases) and specificity of 96 per cent. In this proof-of-principle study, the ESS results were comparable with current intraoperative diagnostic techniques of lymph node assessment.

SPIO Enhanced MR Imaging for the Detection of Metastases in Sentinel Nodes Localized by CT Lymphography in Patients with Breast Cancer.

Abstract Background: Ultrasonography, magnetic resonance (MR) imaging, and computed tomography (CT) may detect nodal metastases in patients with breast cancer, but there is not sufficient accuracy with the conventional methods. Recently, superparamagnetic nanoparticles-enhanced MR imaging has been reported to be a promising improvement for diagnostic imaging of lymph node metastases from various tumors. Moreover, sentinel nodes have been reported to be well-identified using CT lymphography in patients with breast cancer. This study evaluated MR imaging with superparamagnetic iron oxide (SPIO) enhancement for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer, with histopathologic findings as the reference standard.Methods: This study included 102 patients with breast cancer with clinically negative nodes. Each contrast agent was injected intradermally into the skin overlying the breast tumor and in the subareolar region. Sentinel nodes were identified by CT lymphography, and SPIO-enhanced MR imaging of the axilla was performed to detect metastases in the sentinel nodes. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel node biopsy was performed using a combination of dye and radiocolloid. Imaging results were correlated with histopathologic findings.Results: The mean number of sentinel nodes identified by CT lymphography was 1.1 (range 1–3). Twenty-one of 25 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Seventy of 77 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity, and overall accuracy of MR imaging for the diagnosis of sentinel node metastases were 84%, 91%, and 89%, respectively. In four of 10 patients with micrometastases, the metastases were not detected, but all 15 patients with macrometastases were successfully demonstrated. There were no adverse events associated with either CT or MR imaging.Conclusions: SPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT lymphography in patients with breast cancer. Patients with clinically negative nodes may be spared sentinel node biopsy when the sentinel node is diagnosed as disease-free using SPIO-enhanced MR imaging. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1010.

Accuracy of Imprint Cytology for Intraoperative Diagnosis of Sentinel Node Metastases in Breast Cancer

The aim of this study was to determine the accuracy of imprint cytology for the intraoperative diagnosis of sentinel node metastases in patients with breast cancer. Accurate intraoperative diagnosis of sentinel node metastases enables the selection of patients who need axillary lymph node dissection during the same operation. This study included 631 patients with clinical T1 breast cancer with clinically negative nodes. Sentinel nodes were serially sectioned at 2-mm intervals. Imprint cytologic samples were made from all cut surfaces and stained with Papanicolaou staining. Patients with positive sentinel nodes underwent immediate axillary lymph node dissection. Those with negative sentinel nodes diagnosed by intraoperative imprint cytology, but positive by final pathologic results, underwent subsequent axillary lymph node dissection. The results of imprint cytology were compared with the final pathologic results using hematoxylin and eosin staining and immunohistochemistry. In 110 of 130 patients with positive sentinel nodes diagnosed by final pathology, imprint cytology of at least one sentinel node was positive. In 17 of 501 patients with tumor-negative sentinel nodes diagnosed by final pathology, imprint cytology of at least one sentinel node was positive. The sensitivity, specificity, and overall accuracy of imprint cytology for the diagnosis of sentinel node metastases were 84.6%, 96.6%, and 94.1%, respectively. Only 20 (3.2%) patients required a second axillary operation in the present study. Intraoperative imprint cytology is a useful method for evaluating sentinel node metastasis in patients with breast cancer.

Optical biopsy scanner utilising Elastic Scattering Spectroscopy for intra-operative diagnosis of sentinel node metastases in breast cancer.

Optical biopsy scanner utilising Elastic Scattering Spectroscopy for intra-operative diagnosis of sentinel node metastases in breast cancer.

Intraoperative imprint cytology for the diagnosis of sentinel node metastases in breast cancer

Accurate intraoperative diagnosis of sentinel node metastases enables the selection of patients for axillary lymph node dissection, thus avoiding an unnecessary additional operation in patients with false-negative results. The main reason for false-negative results of imprint cytology was poor quality of the imprint samples because of sampling error. False-positive imprint cytology results that lead to an unnecessary axillary lymph node dissection are very rare. Imprint cytology can be recommended for the intraoperative examination of sentinel nodes in breast cancer patients.

The feasibility of intraoperative diagnosis of sentinel lymph node metastases in breast cancer.

The aim of the study was to analyse in detail the feasibility of intraoperative assessment of sentinel lymph nodes in breast cancer. Altogether 139 consecutive breast cancer patients with metastases in axillary sentinel nodes were included in a prospective study. A combination of imprint cytology and frozen section was used as the method of intraoperative diagnosis of sentinel node metastases. The definite postoperative evaluation of the sentinel nodes was taken as the gold standard. The overall sensitivity of intraoperative diagnosis was 83%, reaching 81% if the intraoperative assessment had been limited to the two first retrieved sentinel nodes. False negative (FN) findings were more common in connection with invasive lobular carcinoma (28%) than with invasive ductal carcinoma (8%) (P < 0.01) as well as in connection with micro-metastases, in 38% of the cases, compared to the larger metastases, 6% (P < 0.00005). Intraoperative examination of sentinel lymph nodes enables breast surgery, axillary staging, and treatment in the same operation in a substantial proportion of breast cancer patients. Hospital costs as well as workload in the pathology laboratory may be reduced, limiting the intraoperative assessment to the two first retrieved nodes.