Diagnosis Of Sentinel Lymph Node Research Articles

Identification of sentinel lymph nodes using contrast-enhanced ultrasound in breast cancer patients who underwent neoadjuvant chemotherapy.

59 Background: The aim of this prospective study was to evaluate the feasibility of contrast-enhanced ultrasonography (CEUS) for the identification of sentinel lymph node (SLN) in breast cancer patients with cN0 following neoadjuvant chemotherapy (NAC). Methods: Patients with cN0 following NAC (n=66) received a periareolar injection of SonoVue followed by ultrasound (US) to identify contrast-enhanced SLN before surgery. All patients underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. The identification rate, sensitivity, specificity, accuracy, false negative rate, negative predictive value, positive predictive value was recorded. Results: In almost all cases, the SLNs were easily identified with an identification rate of 98.5 % (65/66). Compared with pathological diagnosis, sensitivity, specificity, accuracy, and false negative rate of CEUS for SLN diagnosis were 66.7%, 95.8%, 78.8%, and 14.3% respectively. Conclusions: Identification of SLN by CEUS is a technically feasible method with an identification rate as high as 98.5%. [Table: see text][Table: see text]

Percutaneous contrast-enhanced ultrasound for localization and diagnosis of sentinel lymph node in early breast cancer

This study assessed the efficacy of percutaneous contrast-enhanced ultrasound (CEUS) in localization sentinel lymph node (SLNs) for biopsy and diagnosis of metastatic SLNs in patients with early breast cancer. From January to November 2017, seventy-five patients with early breast cancer confirmed by pathology were enrolled in this study. CEUS was performed after subdermal injection of ultrasound contrast agent (SonoVue, 2.0 ml in total dose) around the areola on the ipsilateral side of the breast. The contrast-enhanced lymphatic vessels and associated SLNs were observed and traced in real time. The lymphatic vessels and SLN were mapped and labeled on the skin surface. Sentinel lymph node biopsy (SLNB) was performed after injection of 2.0 ml methylene blue at same injection site of SonoVue. The accuracy of percutaneous CEUS localization of SLNs was determined compared to blue dye injection technique. The pathological results under blue dye guided biopsy were used as the reference standard to calculate the sensitivity and specificity of CEUS for the diagnosis of SLNs. A total of 163 SLNs obtained through SLNB following methylene blue tracing in 75 patients. There were 116 SLNs identified by percutaneous CEUS. The difference of detection rates between blue dye and CEUS was statistically significant (Z = −2.651, P = 0.008). The identification rate of SLNs by CEUS was 71.17% (116/163). The accuracy of percutaneous CEUS localization of axillary SLNs was 94.67% (71/75) compared to blue dye-guided biopsy. Among the 116 SLNs detected by percutaneous CEUS, pathologic results showed 51 positive SLNs and 65 negative SLNs whiles CEUS findings indicated 83 positive SLNs and 33 negative SLNs. Only 50 of 83 SLNs had metastasis on pathology, while 33 were detected as false positive. The sensitivity and specificity of CEUS for the diagnosis of metastatic SLN was 98.04%(50/51) and 49.23%(32/65), respectively. Percutaneous CEUS can be used as an effective method to localize the SLNs for guiding SLNB. This method has excellent sensitivity for identifying the SLNs but lower specificity for detecting metastatic SLNs in patients with early stage breast cancer.

Use of Memorial Sloan Kettering Cancer Center nomogram to guide intraoperative sentinel lymph node frozen sections in patients with early breast cancer.

We implemented selective use of frozen section (FS) to optimize accuracy and cost control in the intraoperative diagnosis of sentinel lymph node (SLN) in patients with breast cancer, guided by the Memorial Sloan Kettering Cancer Center (MSKCC) nodal metastasis risk prediction nomogram. Surgical pathology records were reviewed, examining 2582 consecutive biopsies from 2552 patients with breast cancer to compare intraoperative FS diagnoses with postoperative final reports. We calculated sensitivity, specificity, and false-negative rates (FNRs) for various MSKCC risk levels, also analyzing axillary reoperation rates, with and without FS, and the number needed to treat (NNT) to avoid separate axillary lymph node dissection. The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3%, respectively. FNR and MSKCC risk level negatively correlated (r = -0.86; P = .002). Axillary reoperation rate significantly declined if FS was done (FS: 4.0%; no FS: 36.4%; P = .002). In grouping patients by quartile of MSKCC risk, axillary reoperation rates were 16.7%, 25.1%, 38.7%, and 58.7% without FS, compared with 4.3%, 3.2%, 5.6%, 3.3% with FS and NNT correspondingly fell from 8.1 to 4.6, 3.0, and 1.8. A stratified decision-making algorithm based on the MSKCC risk prediction model improved the effectiveness of FS during SLN biopsy to avoid axillary reoperation.

Clinical Value of Single-photon Emission Computed Tomography Combined With Computed Tomography for Sentinel Lymph Node Identification in Melanoma.

Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.

Identification of microRNA expression in sentinel lymph nodes from patients with breast cancer via RNA sequencing for diagnostic accuracy.

Sentinel lymph node (SLN) property assessment (with or without metastasis) is important when deciding the surgery for breast cancer; however, the current diagnosis of SLN metastasis remains to be studied. microRNAs (miRNAs) have been confirmed previously as a molecular marker for the diagnosis, development and prognosis of tumors. However, the detailed role of miRNAs in the diagnosis of SLN metastasis has not been reported. The present study aimed to explore the potential use of miRNAs in the diagnosis of SLN using RNA sequencing (RNA-seq) and a quantitative real-time polymerase chain reaction (qRT-PCR) to compare the expression profiles of miRNAs in patients with breast cancer with or without SLN metastasis. The RNA-seq results revealed that 1993 miRNAs were differentially expressed in patients with breast cancer with SLN metastasis. Among these miRNAs, 1960 were up-regulated and 33 were down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that these differentially expressed miRNAs were associated with tumor growth and metastasis and were also predicted to regulate a series of tumorigenesis and metastasis genes. In particular, the most differentially expressed miRNAs were validated by qRT-PCR, such that miR-200a-3p and miR-96-5p were up-regulated and miR-1-3p and miR-486-3p were down-regulated in patients with breast cancer with SLN metastasis. The findings of the present study suggest that there is an association of miRNAs with SLN metastasis and also that miRNAs function as biomarkers with respect to the choice of therapy and disease prognosis.

Abstract P6-02-16: The efficacy of preoperative pathological features to improve diagnosis accuracy in lymph node metastasis by axillary ultrasound

Abstract Purpose Recently a sentinel lymph node biopsy has been a part of standard surgical procedure instead of an axillary dissection with a mastectomy for breast cancers. It is necessary to make an accurate diagnosis of lymph node metastasis for deciding surgical procedure either a sentinel lymph node biopsy or an axillary dissection. Preoperative ultrasound is one of widely used tools to make a diagnosis of sentinel lymph node. This study presents results regarding preoperative pathological features to improve diagnosis accuracy of sentinel lymph node by preoperative axillary ultrasound. Materials and methods One doctor performed preoperative ultrasound. He used HITACHI HI VISION Ascendus. Axillary lymph node metastasis was suspected when these findings were observed such as partial thickening of lymph node cortex, loss of lymph nodes' hilum, circular swelling shape change and difference compared to a contralateral axillary lymph node. When we suspected axillary lymph node metastasis, we performed fine needle aspiration cytology except other findings such as CT, MRI or physical appearance showed obvious axillary lymph node metastasis. Preoperative core needle biopsies were performed to determine pathologic types and hormone characters. Clinical cases such that ductal carcinoma in situ, lobular carcinoma and ones with primary systemic treatment (neoadjuvant therapy) were excluded from statistical analysis. Results During a study period between April 2015 and December 2017, altogether 662 patients were participated in this study. 304 cases were analyzed by statistical analysis. 268 cases were diagnosed as negative and 36 case as positive in axillary lymph node metastasis by preoperative ultrasound. In the 268 cases 225 cases were diagnosed as negative by sentinel lymph node biopsy during operations (84.0%) but 43 cases were diagnosed as positive (16.0%). 23% cases included less than 20mm micro metastasis (10/43). To investigate correlation between false negative ratio of axillary lymph node metastasis diagnosed by an ultrasound and preoperative pathological features such as hormone receptor, HER2, Ki-67, nuclear grade and subtypes (Luminal, Her2 and triple negative). The false negative ratio was 17.0% vs 11.1% in hormone receptor (positive vs negative, p = 0.434), 14.5% vs 16.0% in HER2 (positive vs negative, p = 0.887), 15.4% vs 19.1% in Ki-67 (<20% vs ≥20%, p = 0.441), 18.4% vs 9.38% in nuclear grade (1 vs 2 and 3, p = 0.997), 11.3% vs 23.8% vs 16.7% vs 16.7% (Luminal A vs Luminal B vs Her2 vs triple negative, p>0.05). Conclusion There were no statistical significant difference between the axillary lymph node metastasis diagnosed by an ultrasound and the preoperative pathological features. However cases categorized in Luminal B by preoperative pathology had relatively high false negative ratio of axillary lymph node metastasis diagnosed by an ultrasound. It is necessary to investigate a way to improve diagnosis accuracy of sentinel lymph node by a preoperative axillary ultrasound. Citation Format: Koike R, Fujita T, Sata N, Shiozawa M, Miyazaki C, Sakuragi M, Shiba S, Tanaka Y. The efficacy of preoperative pathological features to improve diagnosis accuracy in lymph node metastasis by axillary ultrasound [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-16.

Diagnosis comparison of intraoperative imprint cytology and frozen section for sentinel lymph node metastasis in breast cancer

Objective To evaluate whether intraoperative imprint cytology can be used as a diagnostic method of sentinel lymph node metastasis for breast cancer patients in China. Methods A total of 154 breast cancer patients diagnosed histologically as ductal carcinoma in situ or T1-3N0M0 invasive breast cancer who underwent intraoperative sentinel lymph node biopsy from July 2012 to August 2015 in Shanxi Dayi Hospital were enrolled. The sentinel lymph node was detected by using standard dual tracer method. Intraoperative diagnosis was performed with imprint cytology as well as frozen section, and the final diagnosis was assessed by using paraffin pathology after surgery. Results The area under the receiver operator characteristic curve (AUC) for the diagnosis of sentinel lymph node metastasis by intraoperative frozen section and imprint cytology was 0.854 and 0.755, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of imprint cytology were 52.1% (25/48), 99.1% (105/106), 96.2% (25/26), 82.0% (105/128), 84.4% (130/154) respectively, and the corresponding diameters of frozen section were 70.8% (34/48), 100.0% (106/106), 100.0% (34/34), 88.3% (106/120), 90.9% (140/154) respectively. There was no statistically significant difference between the two groups (P > 0.05). The frozen section result was highly consistent with paraffin pathology, with a Kappa value of 0.769 8; while the Kappa value of imprint cytology was 0.587 4, which was moderately consistent with paraffin pathology. Conclusions There is no significant difference between imprint cytology and frozen section in the intraoperative diagnosis of sentinel lymph node metastasis. The consistency between frozen section and paraffin pathology is high. After standardized operations and professional training, imprint cytology can be considered as a substitute of intraoperative sentinel lymph node diagnosis in breast cancer patients. Key words: Breast neoplasms; Sentinel lymph node biopsy; Frozen section; Imprint cytology

Abstract PD2-06: Preoperative diagnosis of sentinel lymph node metastasis using computed tomography lymphography for early breast cancer patients

Abstract Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. This technique represents a minimally invasive, highly accurate method of axillary staging and is an alternative to conventional axillary lymph node dissection. However, an indication of SLN navigation to metastatic disease may lead to misdiagnosis for staging. Recently, SLN identification using computed tomography lymphography (CTLG) has been reported in Japan. This study investigated the value of CTLG for preoperative prediction of SLN status in early breast cancer patients. Patients and method: Between January 2013 and August 2016, 350 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector helical CT scanner. Patients were placed in a supine position with their arms positioned in a cranial direction with CT guidelineattached to the skin at the axilla. We performed an intradermal injection in the periareolar area, using 4 ml of iopamidolwith 1 ml of local anesthetic. The contrasted lymph route and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. We established typical pattern of the lymphography: stain defect of SLN, stagnation of lymphatic route for preoperative diagnosis of metastatic SLN. SLN biopsy was performed using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan) referring to the point by axillary compression technique by plastic device. Intraoperative pathological analysis of SLN was examined, and an axillary lymph node dissection was performed in patients with SLN metastasis pathologically. Results: The median age of the 350 patients was 59 (range 28 – 90) years old. One patient was male and others were female. CTLG were safely performed in all patients. CTLG could visualize lymphatic route and accurately identify SLN in 336 (96.0 %) and 343 (98.0 %) cases, respectively. Lymphatic routes of CTLG were completely consistent with those of fluorescence imaging. The mean number of SLN identified by CTLG was 1.1. Fifty of 350 patients had metastatic SLN pathologically, and 11 of them had micrometastases of SLNs. The accuracy for metastatic diagnosis of SLN using CTLG without micrometastasis was 84.1 %, sensitivity was 82.1 % and specificity was 84.3 %. The positive predictive value was 40.5 % and negative predictive value was 97.3 %. There were no complications associated with SLN identification. Conclusion: CTLG in SLN biopsy has some advantages in that this method is simple and quite useful for obtaining accurate anatomic images of the SLN, lymph vessels, and tumor. CTLG could select the candidate with truly node negative cases in early breast cancer patients, because it predicts lymph node metastasis preoperatively from natural status of the lymphographic image. Citation Format: Abe H, Teramoto A, Tanaka M, Yamasaki K, Yoneda K. Preoperative diagnosis of sentinel lymph node metastasis using computed tomography lymphography for early breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-06.

Novel rapid-immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer

Axillary lymph node status and pathological diagnosis of sentinel lymph nodes (SLNs) is a prognostic factor that influences management of postoperative therapy. Recent reports indicate that one-step nucleic acid amplification and hematoxylin and eosin (HE)-stained frozen sections are effective for intraoperative diagnosis of SLNs. In the present study, we report a rapid-immunohistochemical staining (R-IHC) method that enables intraoperative detection of SLN metastases within 16 min using an anti-cytokeratin antibody. This is the first report on SLN diagnosis using R-IHC in patients with breast cancer. We prospectively examined 160 dissected SLNs from 108 breast cancer patients who underwent surgery at our institute. The dissected SLNs were sectioned and conventionally stained with HE or immunohistochemically labeled with anti-cytokeratin antibody using R-IHC procedures. Intraoperative R-IHC analyses were completed within 16 min, after which diagnoses were made by two pathologists. The total time required for intraoperative diagnosis was about 20 min. In this study series, R-IHC detected four metastatic SLNs that were undetected using conventional HE staining (4/20, 20.0%). Compared with subsequent permanent diagnosis, R-IHC offered 95.2% sensitivity and 100% specificity. These findings indicate R-IHC is a clinically applicable technique that enables precise and quick intraoperative detection of micro- and macrometastasis in breast cancer.

Abstract P2-01-17: The combination of preoperative computed tomography lymphography and intraoperative fluorescence imaging navigation for sentinel lymph node biopsy of early breast cancer patients

Abstract Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. This technique represents a minimally invasive, highly accurate method of axillary staging and is an alternative to conventional axillary lymph node dissection. The combination of the radioisotope and dye-staining methods is the most accurate way to identify SLN. We had reported feasibility and safety of a new technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection without any need for training. Recently, SLN identification using computed tomography lymphography (CTLG) has been reported in Japan. This study investigated a usefulness of the combination of CTLG and fluorescence imaging for SLN biopsy of early breast cancer patients. Patients and method: Between January 2013 and March 2016, 296 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector CT. We performed an intradermal injection in the periareolar area, using 4 ml of contrast agent with 1 ml of local anesthetic. The contrasted lymph route and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. We established typical pattern of the lymphography: stain defect of SLN, stagnation of lymphatic route for preoperative diagnosis of metastatic SLN. During the operation, fluorescence images were obtained using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan). After 0.5 ml dye mixed indigocarmin and ICG was injected intradermally into the periareolar skin, lymphatic route was observed with fluorescence images. SLN biopsy was performed referring to the point by axillary compression technique by plastic device. Intraoperative pathological analysis of SLN was examined. Results: The median age of the 296 patients was 59 (range 28 – 90) years old. One patient was male and others were female. CTLG and fluorescence imaging were safely performed in all patients. CTLG could visualize lymphatic route and accurately identify SLN in 284 (95.9 %) and 290 (98.0 %) cases, respectively, whereas fluorescence imaging identified successfully lymphatic route and SLN in all patients. Lymphatic routes of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p<0.01). Thirty-nine of 296 patients had metastatic SLN pathologically, and 10 of them had micrometastases of SLNs. The accuracy for metastatic diagnosis of SLN using CTLG without micrometastasis was 83.9 %, sensitivity was 82.1 % and specificity was 84.1 %. The positive predictive value was 35.9 % and negative predictive value was 97.7 %. Conclusion: The combination of CTLG and fluorescence imaging revealed easy and effective to detect SLN. The fluorescence imaging was more high detection rate and number of SLN than CTLG. Otherwise, preoperative diagnosis of SLN metastasis using CTLG would be useful to detect negative SLNs. Citation Format: Abe H, Teramoto A, Yamasaki K, Yoneda K, Ogawa M, Kawasaki M, Kameyama M. The combination of preoperative computed tomography lymphography and intraoperative fluorescence imaging navigation for sentinel lymph node biopsy of early breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-17.

Progress of sentinel lymph node detection in breast cancer

Sentinel lymph node (SLN) is the first group of lymph nodes to receive breast lymph nodes and the first group of lymph node metastasis. It can accurately predict the metastatic status of axillary lymph nodes, which is an important reference factor in the diagnosis and treatment of breast cancer. It has become the first choice for early breast cancer staging. The rapid and accurate intraoperative localization and diagnosis of SLN is of great significance for the choice of operation mode and the improvement of therapeutic effect. SLN location and diagnostic methods are still needed to be investigated. This article reviews various methods in clinic recently. Key words: Breast neoplasms; Sentinel lymph node; Locate; Diagnosis

One-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastasis in endometrial cancer

ObjectiveTo evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the diagnosis of sentinel lymph node (SLN) metastasis compared with histopathological examination in patients with endometrial carcinoma. MethodsA total of 94 SLNs from 34 patients with endometrial carcinoma were enrolled. The central 1-mm portion of each node was subjected to semi-serial sectioning, sliced at 200-μm intervals and examined by hematoxylin and eosin and cytokeratin 19 (CK19) immunohistochemical staining, and the remaining tissue was analysed by OSNA using CK19 mRNA. The accuracy of the OSNA assay was evaluated based on histopathological diagnosis. ResultsHistologically, 89 SLNs were determined to be metastasis negative, and the remaining five SLNs were metastasis positive. Using the breast cancer cutoff value for detecting lymph node metastasis (OSNA criteria for breast cancer, >250copies/μl) the sensitivity of the OSNA assay was 100%; specificity was 87.6%; diagnostic accuracy was 88.3%. Discordant results were recorded for 11 of 94 SLNs. In all 11 cases, a positive result was given by the OSNA assay but not by histopathological examination. In two SLNs from the same patient, histopathological examination revealed the presence of benign epithelial inclusions that were CK19 positive; both SLNs yielded a positive result in the OSNA assay (true–false positive). All remaining nine histologically-negative/OSNA-positive SLNs were classified as micrometastasis (+) by the OSNA assay. ConclusionThe OSNA assay shows high sensitivity and specificity, which suggests its utility as a novel tool for the molecular detection of SLN metastasis in patients with endometrial carcinoma.

Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients.

One-step nucleic acid amplification (OSNA) detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive sentinel lymph node diagnosis. The objective of this study was to evaluate the significance of matrix metalloproteinase 9 expression by immunohistochemistry as supporting marker to cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer patients and to relate this expression with clinicopathological data. This study was conducted on fresh sentinel lymph nodes obtained from 40 patients with tumors classified as carcinoma of no special type. The presence of metastatic cells in the slices of lymph nodes was evaluated by immunohistochemistry using antibodies for CK19 and MMP-9. Expression of CK19 and MMP-9 in lymph nodes was also confirmed by means of Western blot analysis. Results indicated that the strongest correlation with CK19 mRNA was displayed by MMP-9, CK19 (by immunohistochemistry, IHC), and nodal metastases (p < 0.001). Higher histological grading also positively correlated with CK19 mRNA, however that correlation was less significant. Since MMP-9 shows very strong correlation with CK19 mRNA in breast carcinoma of no special type metastases, expression of MMP-9 in sentinel lymph nodes should be considered as useful method whenever OSNA analysis is not available.

Cost and Budget Impact Analysis of an Accurate Intraoperative Sentinel Lymph Node Diagnosis for Breast Cancer Metastasis.

Conventional intraoperative sentinel lymph node biopsy (SLNB) in breast cancer (BC) has limitations in establishing a definitive diagnosis of metastasis intraoperatively, leading to an unnecessary second operation. The one-step nucleic amplification assay (OSNA) provides accurate intraoperative diagnosis and avoids further testing. Only five articles have researched the cost and cost effectiveness of this diagnostic tool, although many hospitals have adopted it, and economic evaluation is needed for budget holders. We aimed to measure the budget impact in Japanese BC patients after the introduction of OSNA, and assess the certainty of the results. Budget impact analysis of OSNA on Japanese healthcare expenditure from 2015 to 2020. Local governments, society-managed health insurers, and Japan health insurance associations were the budget holders. In order to assess the cost gap between the gold standard (GS) and OSNA in intraoperative SLNB, a two-scenario comparative model that was structured using the clinical pathway of a BC patient group who received SLNB was applied. Clinical practice guidelines for BC were cited for cost estimation. The total estimated cost of all BC patients diagnosed by GS was US$1,023,313,850. The budget impact of OSNA in total health expenditure was -US$24,413,153 (-US$346 per patient). Two-way sensitivity analysis between survival rate (SR) of the GS and OSNA was performed by illustrating a cost-saving threshold: y≅1.14x-0.16 in positive patients, and y≅0.96x+0.029 in negative patients (x=SR-GS, y=SR-OSNA). Base inputs of the variables in these formulas demonstrated a cost saving. OSNA reduces healthcare costs, as confirmed by sensitivity analysis.

The clinical usefulness of the intraoperative detection of sentinel lymph node metastases by a rapid RT-PCR system in patients with gastric cancer.

The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses. A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer. SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively. The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer.

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

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

Contrast-enhanced ultrasonography in qualitative diagnosis of sentinel lymph node metastasis in breast cancer: A meta-analysis.

This meta-analysis aims to determine the accuracy of contrast-enhanced ultrasonography (CEUS) in the qualitative diagnosis of metastatic sentinel lymph node (SLN) for patients with breast cancer. We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the STATA software, version 12.0 (Stata Corp, College Station, TX, USA). We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR + /LR-), diagnostic odds ratio (DOR) and receiver operating characteristic (SROC) curve. Thirteen articles that met all inclusion criteria were included in this meta-analysis. A total of 876 breast cancer patients were assessed, including 372 patients with metastatic SLN and 504 patients without metastatic SLN. All SLN were histologically confirmed after conducting CEUS. The pooled Sen was 0.80 (95%CI = 0.76-0.84); the pooled Spe was 0.94 (95% CI = 0.91-0.96). The pooled LR + was 6.28 (95%CI = 3.61-10.92); the pooled negative LR - was 0.218 (95% CI = 0.10-0.31). The pooled DOR of CEUS in qualitative diagnosis of SLN metastasis was 49.10 (95% CI = 27.89-86.45). The area under the SROC curve was 0.937 (standard error [SE] =0.0128). Our meta-analysis suggests that CEUS may have high a diagnostic accuracy in testing for metastatic SLN in breast cancer. Thus, CEUS may be a good tool for differential diagnosis between metastatic and non-metastatic SLN.

Investigation of sentinel lymph node biopsy in tongue squamous cell carcinoma of the tongue using One-step Nucleic Acid Amplification (OSNA) assay

Metastasis of cervical lymph node is the most important prognostic factor in oral cancer. In this study, we evaluated the efficacy of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis of sentinel lymph node (SLN) metastasis compared with conventional examination in patients with carcinoma of the tongue. The aim of this study was to investigate availability of the genetic diagnosis in carcinoma of the tongue.

Touch preparations for the intraoperative evaluation of sentinel lymph nodes after neoadjuvant therapy have high false-negative rates in patients with breast cancer.

The use of a touch preparation for intraoperative sentinel lymph node diagnosis has become a preferred method of many pathologists because of its reported high sensitivity and rapid turnaround time. However, after neoadjuvant chemotherapy many lymph nodes have significant treatment-related changes that may affect the diagnostic accuracy of the intraoperative evaluation. To determine the accuracy of touch preparation for the intraoperative diagnosis of metastatic breast carcinoma in the neoadjuvant setting. We reviewed retrospectively the results of intraoperative evaluations for 148 different sentinel lymph nodes from 63 patients who had undergone neoadjuvant chemotherapy for invasive breast cancer at our institution. The intraoperative touch preparation results were compared with the final pathology reports in conjunction with relevant clinical data. Use of touch preparation for the evaluation of sentinel lymph nodes intraoperatively after neoadjuvant therapy was associated with a low sensitivity of 38.6% (95% confidence interval [CI], 24.4-54.5) but high specificity of 100% (95% CI, 96.5-100). There was no difference in sensitivity rates between cytopathologists and noncytopathologists in this cohort (P = .40). Patients with invasive lobular carcinoma and those who had a clinically positive axilla before the initiation of neoadjuvant therapy were the most likely to have a false-negative result at surgery. Intraoperative touch preparations should not be used alone for the evaluation of sentinel lymph nodes in the setting of neoadjuvant therapy for breast cancer because of low overall sensitivity.

Utility of one-step nucleic acid amplification (OSNA) assay in detecting breast cancer metastases of sentinel lymph nodes in a Chinese population

The one-step nucleic acid amplification (OSNA) assay is an innovative method for the diagnosis of sentinel lymph node (SLN) metastases in breast cancer patients. The aim of the present study was to clinically validate the OSNA assay and compare its results with postoperative serial sectioning in a Chinese breast cancer population. A prospective study of 370 consecutive SLNs from 115 patients was conducted at our institution. A total of 311 SLNs underwent OSNA assay analysis. All SLNs were sectioned in approximately 2-mm pieces. OSNA assay and postoperative serial sectioning were performed on alternate divided node samples. The postoperative serial sectioning histology diagnosis was used as the standard. The overall rate of agreement between OSNA assay and the postoperative serial sectioning was 95.2 % [95 % confidence interval (CI) 91.6-96.9 %], with a sensitivity of 83.3 % (95 % CI 66.5-93.0 %), a specificity of 96.7 % (95 % CI 93.7-98.4 %), a positive predictive value of 76.9 % (95 % CI 60.3-88.3 %), and a negative predictive value of 97.8 % (95 % CI 95.0-99.1 %) based on the number of SLNs sampled before the discordant cases analyses. Eleven out of 15 discordant cases can be explained by tissue allocation bias. Our study shows that the OSNA assay is more standardized, objective, and reproducible and can utilize more lymphoid tissue than the traditional pathological examination methods. OSNA can also distinguish between micrometastasis and macrometastasis, thereby enabling us to further study the significance of micrometastasis. Since there is a lack of standardization and reproducibility of pathological examination and diagnostic criteria of the SLNs, we recommend that the OSNA assay can be used in daily clinical diagnostic work.