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Purpose: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). Methods: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. Results: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 pa-tients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no dif-ference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). Conclusion: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pa-thology, as long as axillary radiotherapy is provided. (c) 2021 Published by Elsevier Ltd., Istanbul Breast Society, This project has been supported by the Istanbul Breast Society.

Detection of nodal micrometastasis (tumor size: 0.2–2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.

BACKGROUND Axillary sentinel lymph node biopsy (SLNB) is standard treatment for patients with clinically and pathological negative lymph nodes. However, the role of completion axillary lymph node dissection (cALND) following positive sentinel lymph node biopsy (SLNB) is debated. AIM To identify a subgroup of women with high axillary tumor burden undergoing SLNB in whom cALND can be safely omitted in order to reduce the risk of long-term complications and create a Preoperative Clinical Risk Index (PCRI) that helps us in our clinical practice to optimize the selection of these patients. METHODS Patients with positive SLNB who underwent a cALND were included in this study. Univariate and multivariate analysis of prognostic and predictive factors were used to create a PCRI for safely omitting cALND. RESULTS From May 2007 to April 2014, we performed 1140 SLN biopsies, of which 125 were positive for tumor and justified to practice a posterior cALND. Pathologic findings at SLNB were micrometastases (mic) in 29 cases (23.4%) and macrometastasis (MAC) in 95 cases (76.6%). On univariate analysis of the 95 patients with MAC, statistically significant factors included: age, grade, phenotype, histology, lymphovascular invasion, lymph-node tumor size, and number of positive SLN. On multivariate analysis, only lymph-node tumor size (≤ 20 mm) and number of positive SLN (> 1) retained significance. A numerical tool was created giving each of the parameters a value to predict preoperatively which patients would not benefit from cALND. Patients with a PCRI ≤ 15 has low probability (< 10%) of having additional lymph node involvement, a PRCI between 15-17.6 has a probability of 43%, and the probability increases to 69% in patients with a PCRI > 17.6. CONCLUSION The PCRI seems to be a useful tool to prospectively estimate the risk of nodal involvement after positive SLN and to identify those patients who could omit cALND. Further prospective studies are necessary to validate PCRI clinical generalization.

En cáncer de mama, el ganglio centinela (GC) es el primer ganglio que recibe el drenaje linfático del área de la mama que contiene el tumor, siendo capaz de predecir el estado de los demás ganglios axilares. En los últimos años, múltiples estudios han demostrado el poco impacto que tiene el vaciamiento axilar (VA) en términos de la supervivencia libre de enfermedad (SLE) y la supervivencia global (SG), lo que a su vez ha permitido establecer algunos criterios para omitir la linfadenectomía axilar en pacientes con cáncer de mama en estadios tempranos. Las mujeres con cáncer de mama infiltrante y tumores T1 y T2, con axila clínicamente negativa, son candidatas a la realización del GC. Si el GC es positivo, puede omitirse el VA sólo si se cumplen los siguientes requisitos: 1) manejo quirúrgico del tumor primario con cirugía conservadora o mastectomía, 2) bordes de resección quirúrgicos negativos para malignidad y 3) reporte de patología del GC que muestre hasta dos GC positivos para micro o macrometástasis, sin extensión extracapsular, o con una dimensión de la extensión extracapsular

Objective This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. Study design Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. Results Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. Conclusion Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Background. Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses. Methods. We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves. Results. Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P

Background and Objectives: This study investigated predictive risk factors for cervical nodal recurrence or metastasis in papillary thyroid carcinoma (PTC). Materials and Methods: From September 2014 to February 2015, a total of 321 PTC patients were enrolled retrospectively. Except for 154 N0 patients, the remaining 167 patients were divided into two groups as follows: Group I (n=140), central lymph node (LN) metastasis (pN1a); Group II (n=27), lateral LN metastasis (pN1b, n=23) or LN recurrence (n=4). The patients who had LN metastasis or recurrence underwent selective LN dissection or recurrent LN excision. Results: Central LN metastases were found in 44.0% (142/321) of patients. Two hundred thirty patients (71.7%) were classified as being at low-risk for LN disease, as evidenced by N0 or fewer than five micrometastases. The mean size of central metastatic LNs was 0.37±0.34 cm. A total of 76 patients (46.6%) presented with micrometastasis, and ten (3.1%) presented with extranodal extension (ENE). The multiple/bilateral cancer, Extrathyroidal extension, size of metastatic LN, ENE, high risk LN disease (＞5, macrometastasis, ＞3.0 cm) and high thyroglobulin were significant risk factors in predicting LN recurrence or lateral LN metastasis (p＜0.05) in univariate analysis. Patients with ENE were 10.3 times more at risk for recurrence or metastasis than patients without ENE. Conclusion: We consider the ENE was the most potent risk factors for LN recurrence or lateral LN metastasis in PTC.

Background This study evaluated the usefulness of judgment of central lymph node (LN) metastasis by surgeon's palpation in papillary thyroid cancer. Methods This study included 127 patients who underwent thyroidectomy and central compartment node dissection between October 2014 and February 2015. The criterion for suspicious LNs was hardness. Results Of the 20.5% (28/127) of suspicious for metastatic LNs according to surgeon determination, 92.8% (26/28) were confirmed to be metastatic in the final pathological examinations. Metastatic LNs were found in 38 (38.3%) of 99 patients without suspicious LNs, 29 of whom (76.3%) had micrometastases. The sensitivity, specificity, and positive and negative predictive values for the determination of LN metastasis by a surgeon were 40.6%, 96.8%, 92.9%, and 61.6%, respectively. Conclusion Determination of central LN metastasis by a surgeon's palpation may be useful to evaluate LNs owing to the high specificity and positive predictive values, especially in macrometastasis or high-risk LN disease.

This study aimed to establish intraoperative diagnostic criteria of sentinel lymph node (SLN) micro-/macrometastasis on the basis of tissue rinse liquid-based cytology (TRLBC) in gynecological cancer. We enrolled 214 patients with gynecological cancer who underwent rapid diagnosis of SLN metastasis on the basis of TRLBC from a total of 490 SLNs. For slides that were classified as positive for atypical cells on cytological inspection, we counted the number of clusters (an atypical cell mass consisted of three or more cells) and the number of single cells (an atypical cell other than clusters). Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of predicting SLN micro-/macrometastasis. On cytological inspection, 36 slides were classified as positive for atypical cells, while 21 slides (4.3%) were true positive, 15 (3.1%) were false positive, and 454 (92.6%) were true negative. There were no false negative results in this study. The area under the ROC curve for the number of cluster was superior to that for the number of single cells for distinguishing micro-/macrometastasis from negative/isolated tumor cells (0.86 vs. 0.67, P = 0.032). The optimum cut-off value of the number of clusters was 5 for distinguishing these two categories. TRLBC is a highly sensitive alternative for detecting SLN metastasis as a rapid intraoperative diagnosis. Counting the number of atypical cell clusters might be useful for distinguishing micro-/macrometastasis from isolated tumor cells.

Introduction The purpose of this study was to clarify the clinicopathological features of patients with false-negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. Methods Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2 mm) group and macrometastasis (>2 mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. Results A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non-SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. Conclusions The false-negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false-negative FNAC results.

Introduction: Breast cancer represents the most common type of cancer among women in the world. The presence and extent of axillary lymph node involvement represent an important prognostic factor. Sentinel lymph node biopsy (SLNB) is currently accepted for T1 and T2 with negative axillae (N0); however, many patients with T3-T4b tumors with N0 are often submitted to unnecessarily axillary lymph node dissection. Materials and Methods: This is a retrospective, observational study of patients treated for breast cancer between 2008 and 2015, with T3/T4b tumors and N0, who underwent SLNB. A systematic review of the literature was also carried out in 5 bases. Results: We analyzed 73 patients, and SLNB was negative for macrometastasis in 60.3% of the cases. With a mean follow-up of 45 months, no ipsilateral axillary local recurrence was observed. In the systematic review, only 7 articles presented data for analysis. Grouping these studies with the present series, the rate of N0 was 32.1% for T3 and 61.0% for T4b; grouping all studies (T3 and T4b n = 431) the rate was 32.5%. Conclusions: SLNB in T3/T4b tumors is a feasible and safe procedure from the oncological point of view, as it has not been associated with ipsilateral axillary relapse.

Objective To identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC). Methods Clinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2 mm and >2 mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis. Results Of 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44–73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22–115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33–5.16]). Conclusions Presence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC.

Background Axillary lymph node dissection (ALND) can be avoided in breast cancer patients with low-volume disease in the sentinel lymph nodes (SLNs) according to Z0011 trial. We believe that nomograms developed for predicting non-sentinel lymph node (NSLN) metastases can guide the axillary treatment in patients who do not fully match the criteria of Z0011 study. We identified risk factors and evaluated the performance of three nomograms to predict NSLN status in patients with positive SLNs. Methods Data from 526 breast cancer patients with positive SLNs who underwent ALND at two Australian hospitals from 2002 to 2015 were studied. Univariate and multivariate associations for NSLN metastasis were analysed. Predictive models evaluated were MD Anderson Cancer Centre (MDA), Helsinki University Hospital and Memorial Sloan Kettering Cancer Centre. Results Thirty-nine per cent of patients demonstrated NSLN metastasis. The multivariate analysis identified extranodal extension (OR 3.2, 95% CI 2.07-4.80), tumour size >2 cm (OR 2.5, 95% CI 1.66-3.89), macrometastasis (OR 1.9, 95% CI 1.09-3.47), positive SLN ratio >0.5 (OR 1.7, 95% CI 1.16-2.60) and lymphovascular invasion (OR 1.6, 95% CI 1.09-2.44) as independent predictors for NSLN metastasis. MDA nomogram showed the best discrimination (area under the curve of 0.74) and a 9% false negative rate for predicted probability of NSLN metastasis ≤10%. Conclusion Our results suggest that presence of extranodal extension and tumour size >2 cm may influence the need of further axillary treatment. Conversely, ALND can be safety spared in low risk patients identified by MDA nomogram.

For residual N1 nodal disease following neoadjuvant chemotherapy (NAC) for patients with breast cancer, the optimal local therapy for axilla is an evolving area. We analyzed the long-term results of these patients according to axillary surgical methods using propensity score matching (PSM) to clarify whether omission of axillary lymph node dissection (ALND) is oncologically safe. This was a single institution retrospective study of patients with ypN1 from Asan Medical Center (AMC). We included 324 patients who had undergone axillary surgery with either sentinel lymph node biopsy (SLNB) only or ALND. The patients received NAC at AMC between 2008 and 2013. General indications for ALND included prominent nodes detected clinically before NAC, evident macrometastasis on multiple nodes during SLNB. Patients who had either micrometastasis or macrometastasis in 1 or 2 node(s) were included. SLNB was performed for patients with good responders to NAC with limited nodal burden. Patients were matched for baseline characteristics. After matching, we included 98 patients in each SLNB only group and ALND group respectively. We compared axillary recurrence-free survival (ARFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-free survival (BCSS) according to the surgical method. The median follow-up period was 71 months. Univariate and multivariate analyses revealed no statistically significant differences between the two groups for ARFS, DMFS, OS, and BCSS. After the propensity score matching, no significant statistical differences were observed in 5-year ARFS, DMFS, OS, and BCSS between the SLNB only group and ALND group. SLNB might be a possible option for ALND in patients with breast cancer who have limited axillary node metastasis after NAC without compromising survival outcomes.

PurposeSentinel-lymph-node (SLN) biopsy (SLB) is an efficient and safe axillary surgical approach with decreased morbidity than total axillary lymph node dissection (ALND) in initial patients (T1–T2). Current guidelines strongly suggest avoiding completion of ALND in patients with one or two positive SLNs that will be submitted to whole-breast radiation therapy, but must be done when three SLNs are affected.MethodsWe performed a SEER-based study with breast invasive ductal carcinoma patients treated between 2010 and 2015. Optimal cutoffs of positive LNs predictive of survival were obtained with ROC curves and survival as a continuous variable. Bias was reduced through propensity score matching. Cox regression was employed to estimate prognosis. Nomograms were constructed to analyze the predictive value of clinicopathological factors for axillary burden.ResultsOf 43,239 initial patients that had one to three analyzed LNs, only 425 had two positive LNs and matched analysis demonstrated no survival difference versus pN2 patients [HR: 0.960 (0.635–1.452), p = 0.846]. The positive-to-analyzed LN proportion demonstrated a strong prognostic factor for a low rate (1 positive to ≤1.5 analyzed) [HR = 1.567 (1.156–2.126), p = 0.004], and analysis derived from the results demonstrated that a “negative LN margin” improves survival. Nomograms shows that tumor size is the main factor of axillary burden.ConclusionMacrometastasis of two LNs is a poor prognostic factor, similar to pN2, in SLNB (-like) patients; more extensive studies including preconized therapies must be done in order to corroborate or refute the resistance of this prognostic difference in patients with two macrometastatic lymph nodes within few resected.

Introduction The intraoperative frozen section is a recommended method to detect breast cancer metastasis to axillary sentinel lymph nodes (SLNs); however, frozen section is not widely available and requires an experienced staff. Alternatively, touch imprint cytology (TIC) is a simple and cost-effective technique to detect metastasis. Therefore, in this study, we assessed the diagnostic accuracy of TIC for detecting SLN metastasis and compared it with intraoperative frozen section evaluation. Methodology A retrospective study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, for a duration of two years. A total of 114 patients undergoing surgery for primary breast cancer were included in the study. All patients had clinically and radiologically negative axillary lymph nodes. SLN sampling was done using radioactive dye and sent for intraoperative consultation. The SLNs were sliced at 4-mm intervals and two TIC slides and three step-levels for frozen section were prepared, and the results were compared with final (paraffin) section histology. Results The sensitivity, specificity, and diagnostic accuracy of TIC was 83.7%, 98.5%, and 92.1%, respectively. Alternatively, the sensitivity, specificity, and diagnostic accuracy of frozen section was 93.9%, 100%, and 97.4%, respectively. The sensitivity of TIC and frozen section for detecting micrometastasis was 14.3% and 57.1%, respectively, with a diagnostic accuracy of 90.3% and 95.8%, respectively. Alternatively, with respect to macrometastasis, the sensitivity and specificity of TIC were 95.2% and 98.5%, respectively, while the sensitivity and specificity of frozen section were 100%. Conclusion TIC is a quick and effective technique for detecting breast cancer metastasis in axillary SLNs. Although frozen section had an overall higher sensitivity than TIC, the sensitivity of TIC for detecting macrometastasis was comparable to the frozen section. Therefore, we conclude that TIC is a good alternative to the frozen section in facilities where the frozen section is not available.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis., El objetivo de este estudio fue evaluar la eficacia de la amplificación de ácido nucleico en un solo paso (OSNA) para la detección de metástasis en el ganglio linfático centinela (GC) en comparación con la ultraestadificación patológica estándar en pacientes con cáncer de endometrio (CE) en estadio temprano. Se incluyeron en el estudio un total de 526 SLN de 191 pacientes con EC, y 379 SLN (147 pacientes) fueron evaluados por ambos métodos, OSNA y ultraestadificación patológica estándar. La porción central de 1 mm de cada ganglio linfático se sometió a un seccionamiento semiserie a intervalos de 200 μm y se examinó mediante hematoxilina-eosina e inmunohistoquímica con CK19; el tejido restante fue analizado por OSNA para ARNm de CK19. El ensayo OSNA detectó metástasis en el 19,7 % de los pacientes (14,9 % micrometástasis y 4,8 % macrometástasis), mientras que la ultraestadificación patológica detectó metástasis en el 8,8 % de los pacientes (3. 4% micrometástasis y 5,4% macrometástasis). Usando el valor de corte establecido para detectar metástasis SLN por OSNA en EC (250 copias/μL), la sensibilidad del ensayo OSNA fue del 92 %, la especificidad fue del 82 %, la precisión diagnóstica fue del 83 % y el valor predictivo negativo fue del 99 % Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico.

Objective This study aimed to establish intraoperative diagnostic criteria of sentinel lymph node (SLN) micro-/macrometastasis on the basis of tissue rinse liquid-based cytology (TRLBC) in gynecological cancer. Methods We enrolled 214 patients with gynecological cancer who underwent rapid diagnosis of SLN metastasis on the basis of TRLBC from a total of 490 SLNs. For slides that were classified as positive for atypical cells on cytological inspection, we counted the number of clusters (an atypical cell mass consisted of three or more cells) and the number of single cells (an atypical cell other than clusters). Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of predicting SLN micro-/macrometastasis. Results On cytological inspection, 36 slides were classified as positive for atypical cells, while 21 slides (4.3%) were true positive, 15 (3.1%) were false positive, and 454 (92.6%) were true negative. There were no false negative results in this study. The area under the ROC curve for the number of cluster was superior to that for the number of single cells for distinguishing micro-/macrometastasis from negative/isolated tumor cells (0.86 vs. 0.67, P = 0.032). The optimum cut-off value of the number of clusters was 5 for distinguishing these two categories. Conclusions TRLBC is a highly sensitive alternative for detecting SLN metastasis as a rapid intraoperative diagnosis. Counting the number of atypical cell clusters might be useful for distinguishing micro-/macrometastasis from isolated tumor cells.

Introduction Lymph node metastases are considered a major risk factor in endometrial carcinoma patient management and nodal assessment is an integral part of staging. While still under investigation sentinel node biopsy has been established in many centers. It has been shown that histopathologic ultrastaging leads to an increased detection of isolated tumor cells (ITC) and micrometastases (MIC). However, the clinical impact of ITC and MIC is not yet clearly defined. The aim of this study was to retrospectively perform histopathologic ultrastaging in a large series of endometrial carcinoma patients all of which have been treated at the Tuebingen University Women’s Hospital. Method Patients with sentinel node biopsy during endometrial carcinoma surgery were identified. All cases with negative sentinel nodes, were submitted to retrospective histopathologic ultrastaging (5 × 100μm intervals followed by 500μm sections and immunohistochemical pancytokeratine staining of the entire lymphnode). Results A total of n=159 cases was available, of which in 5/159 (3.0%) case positive nodes were detected during initial routine pathology workup (pT1a,G3: n=1; pT1b,G1: n=1; pT1b,G3: n=2; pT2,G2: n=1). After retrospective ultrastaging additional micrometastases were identified in n=3 cases (pT1a,G1; pT1a,G2; pT1a,G3), isolated tumor cells in n=2 cases (pT1a,G3; pT1b,G3), a macrometastasis was revealed in one case (pT1b,G3). Overall 11/159 cases (6,7%) were finally reported positive. Conclusion In our cohort histopathologic ultrastaging of endometrial carcinoma sentinel nodes led to a substantially increased detection rate of nodes with isolated tumor cells, micro- and macrometastases. We suggest that histopathologic ultrastaging should be mandatory in endometrial carcinoma sentinel lymph node workup.

Aims To determine if there is any correlation between the number of positive non-sentinel lymph nodes (NSLN) and the mRNA copy numbers of cytokeratin 19 receptor on one step nucleic acid amplification (OSNA) in the sentinel lymph node (SLN). Methods An 8-year retrospective study of consecutive patients who had primary surgery and sentinel node biopsy for breast cancer from January 2011 to December 2018 was carried out. All these patients had intra-operative analysis of sentinel lymph nodes by OSNA. Patients who had neoadjuvant chemotherapy or neoadjuvant endocrine therapy were excluded. Results There were 1159 patients with an age range of 24 to 90 years and a mean age of 63 years in this study. A total of 1324 SLNs were analyzed by OSNA. Macrometastasis was found in 120 patients and they underwent axillary lymph node dissection (ALND). A total of 2405 NSLNs were analyzed. Of the patients who had ALND, 51 (43%) patients had negative NSLNs and 69 (57%) had positive NSLNs. The mean mRNA copy numbers respectively for the 2 groups were 853,665 and 609,855. The difference between the means is not statistically significant (P = 0.82). Also the Receiver Operating Characteristic (ROC) Curve of the total CK-19 mRNA copy number for both groups-negative and positive NSLN were almost identical (Figure 3) indicating mRNA copy numbers cannot be used to discriminate between positive and negative non-sentinel lymph nodes. Conclusion It is clear from our study that in patients who have ALND due to macromets on OSNA, there is no correlation between the total tumor load as represented by mRNA copy numbers and the likelihood of positive non-sentinel lymph nodes. We therefore cannot rely solely on the mRNA copy numbers to decide on ALND.

Background and objectives The purpose of this study was to find out the risk factors associated with non-sentinel lymph node metastasis and determine the incidence of non-sentinel lymph node metastasis according to risk groups in sentinel lymph node (SLN)-positive endometrial cancer patients. Methods Patients who underwent at least bilateral pelvic lymphadenectomy after SLN mapping were retrospectively analyzed. Patients were categorized into low, intermediate, high-intermediate, and high-risk groups defined by ESMO-ESGO-ESTRO. Results Out of 395 eligible patients, 42 patients had SLN metastasis and 16 (38.1%) of them also had non-SLN metastasis. Size of SLN metastasis was the only factor associated with non-SLN metastasis (p = .012) as 13/22 patients with macrometastasis, 2/10 with micrometastasis and 1/10 with isolated tumor cells (ITCs) had non-SLN metastasis. Although all 4 metastases (1.8%) among the low-risk group were limited to SLNs, the non-SLN involvement rate in the high-risk group was 42.9% and all of these were seen in patients with macrometastatic SLNs. Conclusions Non-SLN metastasis was more frequent in higher-risk groups and the risk of non-SLN metastasis increased with the size of SLN metastasis. Proceeding to complete lymphadenectomy when SLN is metastatic should further be studied as the effect of leaving metastatic non-SLNs in-situ is not known.

Background Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer. Methods We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter > 2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted. Results For SLN biopsy (SLNB), a median of 2 (range, 1–8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter > 10 mm than in those with diameter ≤ 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p Conclusions Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.

Objective: To evaluate the oncological outcomes of patients with low-volume metastasis compared to those with macrometastasis and negative nodes in endometrial cancer. Methods: A single institutional retrospective study was carried out, which included all patients with endometrial cancer who underwent surgical treatment between January 2007 and December 2016. We analyzed the progression-free survival (PFS) and overall survival (OS) of all patients after sentinel node biopsy and full nodal surgical staging according to their final pathological nodal status, focusing on the impact of the size of nodal metastasis. Results: A total of 270 patients were operated on during the study period, among them, 230 (85.2%) patients underwent nodal staging. On final pathology, 196 (85.2%) patients had negative lymph nodes, low-volume metastasis (LVM) was present in 14 (6.1%) patients: 6 (2.6%) patients had isolated tumor cells (ITCs) and 8 (3.5%) patients presented just micrometastasis, additionally, 20 (8.7%) patients presented macrometastasis. After a median (range) follow-up of 60 (0&ndash, 146) months, patients with macrometastasis showed a significantly worse PFS compared to LVM and node-negative patients (61.1% vs. 71.4% vs. 83.2%, respectively, p = 0.018), and similar results were obtained for 5-year OS (50% vs. 78.6% vs. 81.5%, respectively, p &lt, 0.001). Half of the patients presenting LVM did not receive adjuvant treatment. Moreover, LVM had a moderate nonsignificant decrease in 5-year PFS compared to node-negative patients. Conclusions: Patients with endometrial cancer and low-volume nodal metastasis demonstrated a better prognosis than those presenting macrometastasis. Low-volume metastasis did not show worse oncological outcomes than node-negative patients, although there was a slight decrease in progression-free survival.

IntroductionThe objective of this study was to compared standard ultra-staging (SU) with one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis in women with apparent uterine-confined endometrial cancer.MethodsAll women underwent SLN identification with complete surgical staging. All SLNs were cut perpendicular to the long axis and two adjacent 5 µm sections were cut at each of two levels 50 µm apart. At each level, one slide was stained with hematoxylin and eosin and the other with immunohistochemistry using the AE1/AE3 anti-cytokeratin antibody, as well as one negative control slide for a total of five slides per block. For OSNA analysis, the 2 mm sections of the lymph nodes were homogenized to form a lysate. The lysate was then centrifuged and inserted into the RD 100i instrument where the isothermal amplification of CK19 mRNA was executed.ResultsOf the 396 patients included in the retrospective analysis, 214 were in the SU group, and 182 in the OSNA group. Overall 869 SLNs were identified (490 SU, 379 OSNA). Sixty patients exhibited SLN metastasis (34 SU, 26 OSNA). Macrometastasis, micrometastases, and isolated tumor cells (ITC) were 5.1%, 4.1%, and 0.2%, respectively, in the US group, and 2.4%, 6.3%, and 0.1%, respectively, in the OSNA group (p=0.022).ConclusionsThe OSNA assay detected a higher rate of micrometastasis and a lower rate of macrometastasis and ITC when compared with SU. The clinical and prognostic impact of ITC is debatable and controversial. Further studies are needed to clarify the respective roles of the OSNA and SU methods, and the possible role of ITC in the prognosis of patients with apparent early-stage endometrial cancer.

An application of FTIR spectroscopic imaging for the identification and visualization of early micrometastasis from breast cancer to lungs in a murine model is shown. Spectroscopic and histological examination is focused on lung cross-sections derived from animals at the early phase of metastasis (early micrometastasis, EM) as compared to healthy control (HC) and late phase of metastasis (advanced macrometastasis, AM) using murine model of metastatic breast cancer with 4T1 cells orthotopically inoculated. FTIR imaging allows for a detailed, objective and label-free differentiation and visualization of EM foci including large and small micrometastases as well as single cancer cells grouped in clusters. An effect of the EM phase on the entire lung tissue matrix as well as characteristic biochemical profiles for HC and advanced macrometastasis were determined from morphological and spectroscopic points of view. The extraordinary sensitivity of FTIR imaging toward EM detection and discrimination of AM borders confirms its applicability as a complementary tool for the histopathological assessment of the metastatic cancer progression.

We compared the performance of near-infrared imaging using indocyanine green (ICG) with the radioisotope (ISO) method to detect sentinel lymph nodes (SLNs) in breast cancer, to analyze predictive factors for negative ICG identification. The study included 122 patients who underwent sentinel lymph node biopsy (SLNB) using the combined ISO and ICG technique for primary breast cancer. We assessed the putative association between pathologic/clinical variables and ICG failure to detect SLNs. The ISO identification rate was 96.7% and ICG identification 81.9%. Overweight patients or presence of macrometastasis in SLNB were associated with the risk of ICG failing to detect SLNs (P = 0.02).

Background The aim of this study is to elucidate the clinicopathological significances, including the prognostic role, of metastatic lymph node ratio (mLNR) and tumor deposit diameter in papillary thyroid carcinoma (PTC) through a retrospective review and meta-analysis. Methods We categorized the cases into high (≥ 0.44) and low mLNR (< 0.44) and investigated the correlations with clinicopathological parameters in 64 PTCs with neck level VI lymph node (LN) metastasis. In addition, meta-analysis of seven eligible studies was used to investigate the correlation between mLNR and survival. Results Among 64 PTCs with neck level VI LN metastasis, high mLNR was found in 34 PTCs (53.1%). High mLNR was significantly correlated with macrometastasis (tumor deposit diameter ≥ 0.2 cm), extracapsular spread, and number of metastatic LNs. Based on linear regression test, mLNR was significantly increased by the largest LN size but not the largest metastatic LN (mLN) size. High mLNR was not correlated with nuclear factor κB or cyclin D1 immunohistochemical expression, Ki-67 labeling index, or other pathological parameters of primary tumor. Based on meta-analysis, high mLNR significantly correlated with worse disease-free survival at the 5-year and 10-year follow-up (hazard ratio [HR], 4.866; 95% confidence interval [CI], 3.527 to 6.714 and HR, 5.769; 95% CI, 2.951 to 11.275, respectively). Conclusions Our data showed that high mLNR significantly correlated with worse survival, macrometastasis, and extracapsular spread of mLNs. Further cumulative studies for more detailed criteria of mLNR are needed before application in daily practice.

Sentinel node (SN) concept is being applied to early gastric cancer. However, when SNs are positive for metastasis, it is unclear how often LNs in other LN basins show metastasis. We aimed to investigate LN metastasis possibility in LN basins without SNs (non-SN basins). We determined risk factors for metastasis in non-SN basins and identified a prediction model for non-SN basin metastasis using classification and regression tree (CART) analysis. We enrolled 550 patients who were diagnosed with cT1N0M0 or cT2N0M0 gastric cancer with a single lesion and underwent SN mapping. We adopted a dual-tracer method using a radioactive colloid and blue dye to detect SNs. Of all, 45 (8.2%) patients had SN metastasis; we divided them into two groups: LN metastasis positive and LN metastasis negative in non-SN basins. Univariate analysis showed that the groups differed significantly regarding lymphatic invasion (p = 0.007), number of identified SNs (p = 0.032), and macrometastasis in SN basins (p = 0.005). The CART decision tree for predicting LN metastasis in non-SN basins had area under the curve value of 0.86. Moreover, there were significantly differences in cancer-specific survival (CSS) between the two groups (p = 0.028). Macrometastasis in SN basins, lymphatic invasion, and number of identified SNs ≥ 5 are risk factors for LN metastasis in non-SN basins among gastric cancer patients. We identified a prediction model with CART analysis; patients with macrometastasis in SN basins and lymphatic invasion were considered to be at the highest risk for LN metastasis.

Recent studies suggested that ALND (axillary lymph node dissection) can be avoided in breast cancer patients with limited SLN (sentinel lymph node) metastasis. However, these trials included only several invasive lobular carcinoma (ILC) cases, and the validity of omitting ALND for ILC remains controversial. Here, we examined whether omitting ALND is feasible in ILC treatment. A total of 3771 breast cancer patients underwent surgery for breast cancer at the Aichi Cancer Center Hospital between January 2006 and December 2015. We excluded patients with neoadjuvant therapy or without axillary management, and identified 184 ILC patients and 2402 invasive ductal carcinoma (IDC) patients. We compared SLN and non-SLN metastasis rates and the number of total ALN metastases between the ILC and IDC cohorts, and we examined the factors that influenced non-SLN metastasis in the SLN micrometastasis group. SLN biopsies were performed in 171 (93%) ILC and 2168 (90%) IDC cases, and 31 (18%) ILC and 457 (21%) IDC cases were SLN micrometastasis and macrometastasis (p = 0.36). Among SLN macrometastasis patients, 17 (68%) ILC cases and 163 (46%) IDC cases showed non-SLN metastasis (p = 0.03). The number of non-SLN metastases was greater in ILC cases compared with IDC cases. Multivariate analysis showed that ILC was the influential factor predicting non-SLN metastasis in patients with SLN macrometastasis. ILC cases had more non-SLN metastasis than IDC cases among SLN-positive cases, and ILC was an important factor for the prediction of non-SLN positivity in SLN macrometastasis cases. Omitting ALND for ILC with positive SLNs requires more consideration.

In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I and II. We performed a monocentric retrospective study of 37 consecutive cases with Merkel cell carcinoma stage I to III treated with a combination of surgery and adjuvant radiation to evaluate progression-free and overall survival. The median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary tumours, of which 13 had negative sentinel lymph node biopsy (IA n = 10 and IIA n = 3) and 18 no sentinel lymph node biopsy (IB n = 15 and IIB n = 3), 2 tumours with positive sentinel lymph node biopsy (IIIA) and 4 with local macrometastasis (IIIB). The median age was 71 years and the median follow-up was 60.4 months. The 5-year progression-free survival was 83.8% and 5-year disease-specific survival was 95.7% (overall survival 93.0%). So far, our results show a high survival rate with combined treatment of surgery and adjuvant radiotherapy in early tumour stages of Merkel cell carcinoma.

The aim of the present study was to assess the sensitivity, specificity and practicality of using a one-step nucleic acid amplification (OSNA) assay during breast cancer staging surgery to predict and discriminate between at least 2 involved nodes and more than 2 involved nodes and facilitate the decision to provide axillary conservation in the presence of a low total axillary node tumour burden. A total of 700 consecutive patients, not treated with neo-adjuvant chemotherapy, received intraoperative sentinel lymph node (SLN) analysis using OSNA for cT1-T3 cN0 invasive breast cancer. Patients with at least one macrometastasis on whole-node SLN analysis underwent axillary lymph node dissection (ALND). The total tumour load (TTL) of the macrometastatic SLN sample was compared with the non-sentinel lymph node (NSLN) status of the ALND specimen using routine histological assessment. In total, 122/683 patients (17.9%) were found to have an OSNA TTL indicative of macrometastasis. In addition, 45/122 (37%) patients had NSLN metastases on ALND with a total positive lymph node burden exceeding the American College of Surgeons Oncology Group Z0011 trial threshold of two macrometastatic nodes. The TTL negative predictive value was 0.975 [95% confidence interval (CI), 0.962–0.988]. The area under the curve for the receiver operating characteristic curve was 0.86 (95% CI, 0.81–0.91), indicating that SLN TTL was associated with the prediction (and partitioning) of total axillary disease burden. OSNA identifies a TTL threshold value where, in the presence of involved SLNs, ALND may be avoided. This technique offers objective confidence in adopting conservative management of the axilla in patients with SLN macrometastases.

Background Sentinel lymph node (SLN) biopsy is the current prognostic tool for clinically node-negative breast cancer patients. If the SLN reveals macrometastasis, axillary lymph node dissection (ALND) is recommended. However, the use of ALND in patients with micrometastasis is debated. The objective of this study was to assess the utilization of ALND in the treatment of micrometastatic breast cancer. Methods An IRB approved, retrospective study of a pooled dataset of breast cancer patients with micrometastatic disease on SLN biopsy was performed. Patients diagnosed from 1999-2016 were identified via query of a single-institution National Comprehensive Cancer Network (NCCN) breast cancer database as well as a prospective tumor board. Results A total of 91 patients were diagnosed with micrometastatic nodal disease. The median age at diagnosis was 56 y (range: 31-85); median follow-up time was 47 mo (range: 0-203 mo). 42/91(46.2%) patients had ALND of which 37/42 (88.1%) were a second operation; 3/42(7.1%) patients had additional positive nodes found at ALND. 44/91 (48.4%) patients received radiation. 7/91 (7.7%) patients had a recurrence, 5/7 local, including one axillary (2.1%; patient declined ALND). Conclusions Given that the risk of lymphedema after ALND ranges between 20%-53%, the morbidity of ALND may far exceed the likelihood of detecting further nodal involvement in women with micrometastatic disease: 7.1% in this series.

We aimed to evaluate whether obese women experience more advanced invasive breast carcinoma (IBC) with a higher number of involved lymph nodes, higher range of axillary lymph node ratio (LNR) and presence and size of extracapsular extension as it may have an impact on prognosis and management. 245 patients diagnosed with IBC were divided into normal weight (NW), overweight (OW) and obese (OB) groups. Patients were divided into high range of LNR (LNR over or equal to 0.2) and low LNR (LNR less than 0.2). The extracapsular extension dimensions were measured on the original slides of each case and grouped into ≤ 1 mm and > 1 mm. 84 patients (33.07%) were OW, 72 (29.38%) OB and 91 (37.14%) NW. 45.7% of cases had macrometastasis in the axillary lymph nodes. NW patients had significantly fewer metastatic lymph nodes (p = 0.05) than in the OW/OB groups. There was no statistically significant difference between BMI groups according to the LNR (p = 0.66). Out of 111 cases with macrometastasis, 58 cases (52.25%) had extracapsular extension (ECE) (11.7% NW, 24.32% OW and 16.22% OB). Significantly more OW patients presented extranodal invasion (p = 0.04). We found no statistically significant relationship between the extracapsular extension diameter and BMI groups (p = 0.1).

Metastasis and growth in neoplastic lesions requires the multistep regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of primary tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; ≤2 mm in size), and 82 of LN macrometastasis (LN-Mac; ≥10 mm in size). Afterwards we evaluated the expression of nine molecules (epidermal growth factor receptor, fibroblast growth factor receptor 2, CD44, aldehyde dehydrogenase 1, Podoplanin, E-cadherin, S100A4, geminin, and ezrin) in matched PT, ILT, LN-Mic, and LN-Mac from 23 of these cases. The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of tumor cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (P

Introduction/Background Endometrial cancer is the most common gynecologic malignancy in Spain. Surgical evaluation of the lymph nodes is important in these patients. Traditionally, lymph node assesment required complete pelvic and paraaortic lymphadenectomy. Nowadays, Sentinel lymph node (SLN) mapping is gaining wide difussion with the goal of reducing the high morbidity associated with complete lymphadenectomy. The detection of nodal metastasis is a good marker of poor prognosis and will influence the decision of giving adyuvant therapy. Methodology Patients were surgically staged by two different surgeons in the same institution. The cohort includes patients diagnosed of endometrial cancer at early- stages from 2017–2019 who underwent a SLN mapping. Indocyanine green (ICG), an methylene Blue in some cases, was injected into the uterine cervix at 3 and 9 o’clock. Fluorescence Imaging was used to visualize ICG tracer. Results Twenty patients were enrolled. The median age was 61.35 years. The mean body-mass index(BMI) was 28.84. The overall detection rate (DR) of SLN mapping was 80% (16/20) with a 55% (11/20) bilateral detection. The addition of methylene blue to ICG did not increase the DR. No nodal metastasis were found. Five complete pelvic lymphadenectomies and three para-aortic were perfomed laparoscopically when >50% myometrial infiltration was identified. Lymph node macrometastasis were found in 20% (1/5). Conclusion Further studies are needed to standarize the SNL mapping as an alternative to traditional lymphadenectomy. Our results are similar to the ones published in the literature. Nevertheless, much larger sample size is needed to to draw any relevant conclusions. Disclosure Nothing to disclose.

Introduction/Background Complete cytoreduction followed by combination of platinum-taxane chemotherapy remains standard treatment for epithelial ovarian cancer (EOC). The role of adding systematic lymphadenectomy to cytoreduction procedures in advanced EOC has been a topic of debate. Recently, the LION trial showed that systematic lymphadenectomy after maximal cytoreduction in absence of bulky nodes does not improve survival and may cause additional harm. The aim of this study is to describe the rate of radiological and histological positive lymph nodes in primary or interval cytoreduction and to estimate the impact that application of the conclusions of LION trial would have in our centre. Methodology A consecutive series of 54 patients with newly diagnosed EOC operated between 2017 and 2018 at Dr. Josep Trueta University Hospital was analysed. Data were retrieved from the departmental database and hospital electronic medical records. Results 42 patients (77%) were diagnosed at III/IV FIGO stage and underwent cytoreductive surgery. Of them, 46.5% had primary cytoreductive surgery, while 53.5% underwent interval cytoreduction surgery. All patients had a routinely performed preoperative CT-scan and the presence and pattern of bulky nodes was analysed. The most frequent localization of bulky nodes in CT-scan was paraaortic. After neo-adjuvant chemotherapy, bulky nodes responded in almost all cases. Systematic pelvic lymphadenectomy was performed in 80.4% of cases, and paraaortic lymphadenectomy in 78.3%. The pathological involvement of lymph nodes was analysed. Only one case of interval cytoreduction had nodal macrometastasis, which was presurgical identificated on CT-scan. Conclusion CT-scan is a good predictor for nodal macrometastasis. In absence of bulky nodes and as a result of applying LION conclusions, near 70% of lymphadenectomies in primary cytoreduction and near 95% in interval cytoreduction could be avoided. Careful selection of patients and discussion of CT-scans in multidisciplinary preoperative tumor conference is crucial to avoid unnecessary procedures and to reduce surgical complicactions. Disclosure Nothing to disclose.

Introduction/Background Since the risk of recurrence is low in early-stage cervical cancer, any assessment of prognostic importance of micrometastases (MIC) requires a large cohort. The aim of the study was to retrospectively analyze a large group of patients treated at a single site where sentinel lymph node (SLN) has been used in the management of cervical cancer since 2004 and which has an intensive protocol for SLN pathological ultrastaging. Methodology Patients with stage T1a - T2b cervical cancer treated by primary surgery with curative intent, who had common tumor types, at least unilateral SLN detection, and who were treated between 01/2007 - 12/2016 were included in the study. Radical surgery was abandoned if metastasis in SLN was detected by frozen section. All SLN were processed by an intensive protocol for SLN ultrastaging (entire SLN processed, 2 sections (H&E/cytokeratin) in 150 µm intervals from each block). Results The analysis included data from 234 patients (table 1). Adjuvant treatment was given to 79% of patients with macrometastasis (MAC), 77% with MIC, and 11% with isolated tumor cells (ITC). Within the median follow-up of 67 months 29 recurrences occurred. The recurrence rate of patients with negative LN, with MAC, MIC or ITC reached 9%, 29%, 35% and 22% respectively. Table 2 shows parameters significant for the risk of recurrence. Kaplan-Meier curves for PFS were significantly different for cases with MAC and MIC in comparison to LN-negative cases (figure 1). Conclusion The presence of MIC in SLN was associated with significantly decreased PFS, similar to MAC. There was a similar trend for ITC, but it did not reach significance due to low numbers. Patients with MIC and MAC should be managed identically and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer. Disclosure Acknowledgements This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Research Council (No 16-31643A). None of the authors declare any conflict of interest.

Objectives Ultra-staging (US) of sentinel lymph nodes (SLN) increases the detection of nodal metastases. US protocols vary among gynecologic pathologists, and internationally accepted guidelines are still not available. This study compares two US protocols (US-A vs US-B) in early stage cervical (CC) and endometrial cancers (EC) (table 1). Methods We retrospectively evaluated patients with clinical stage I endometrial cancer (EC) or stage IA-IB1 cervical cancer (CC) who underwent primary surgery with SLN biopsy from November 2010 to October 2017. Results 229 patients were analyzed (161 ECs and 68 CCs). The rate of positive node disease was: 22% with US-A protocol and 12% with US-B protocol (p=0.09) for EC patients; 22% and 10% (p=0.18) for CC patients. Macrometastasis, micrometastases, and ITC were 31%, 61% and 8%, respectively with US-A protocol; 43%, 40% and 17%, respectively with US-B protocol (p=0.272). Mean size of nodal metastasis was 5.4±6.3 mm for US-A and 3.2±4.3 mm for US-B protocol (p=0.09). On multivariate analysis including grade and LVSI, the US method was not associated with the detection of nodal metastases. Conclusions Approximately 50% of the nodal metastases detected by US of SLNs were low-volume metastases. In this study, the detection of positive node disease was not associated with the type of US protocol used. Larger multicenter prospective studies are advisable to confirm these results.

The surgical approach to the axilla in breast cancer has been a controversial issue for more than three decades. Data from recently published trials have provided practice-changing recommendations in this scenario. However, further controversies have been triggered in the surgical community, resulting in heterogeneous diffusion of these recommendations. The development of clinical guidelines for the management of the axilla in patients with breast cancer is a work in progress. A multidisciplinary team discussion was held at the research hospital Policlinico San Matteo from the Universita degli Studi di Pavia with the aim to update recommendations for the management of the axilla in patients with breast cancer. An evidence-based approach is presented. Our multidisciplinary panel determined that axillary dissection after a positive sentinel lymph node biopsy may be avoided in cN0 patients with micro/macrometastasis to ≤2 sentinel nodes, with age ≥40y, lesions ≤3 cm, who have not received neoadjuvant chemotherapy and have planned breast conservation (BCS) with whole breast radiotherapy (WBRT). Cases with gross (>2 mm) ECE in SLNs are evaluated on individual basis for completion ALND, axillary radiotherapy or omission of both. Patients fulfilling the criteria listed above who undergo mastectomy, may also avoid axillary dissection after multidisciplinary discussion of individual cases for consideration of axillary irradiation. Women 70 years or older with hormone receptors positive invasive lesions ≤3 cm, clinically negative nodes, and serious or multiple comorbidities who undergo BCS with WBRT, may forgo axillary staging/surgery (if mastectomy or larger tumor, comorbidities and life expectancy are taken into account).

Background The ACOSOG Z0011 trial demonstrated safe omission of axillary lymph node dissection (ALND) in patients with one or two positive sentinel lymph nodes (SLNs) receiving breast conservative surgery, followed by whole breast irradiation and adjuvant systemic treatment. This study aims to evaluate the exportability of the ACOSOG Z0011 criteria in an Asian/Chinese cohort residing in Hong Kong. Methods Retrospective analysis of a prospectively maintained database in a University affiliated tertiary breast centre was performed from June 2014 to May 2019. All breast cancer patients with no palpable adenopathy before surgery, one or more positive sentinel lymph nodes on histological examination and no prior neoadjuvant systemic treatment were recruited. Patients were grouped as eligible or ineligible according to the ACOSOG Z0011 criteria. The eligible group was compared with the sentinel alone group in the ACOSOG Z0011 cohort. Results Two hundred and forty-eight patients were recruited into the study. Sixty patients (24%) met the ACOSOG Z0011 criteria and could potentially avoid ALND. A higher percentage of clinical T2 tumors were observed in our eligible group than in the ACOSOG Z0011 trial (P=0.002). The histological subtype, tumor grade, estrogen receptor (ER)/progestogen receptor (PR) status and lymphovascular invasion status did not differ. There was no statistically significant difference in the proportion of SLN micrometastasis and macrometastasis between the two groups. Conclusions This study demonstrated clinical similarities between our eligible cohort and the ACOSOG Z0011 cohort, which confirms exportability of the ACOSOG Z0011 criteria to a subset of population in Hong Kong.

Background and objectives The Axillary Lymph Node Dissection (ALND) is the standard treatment in patients with invasive breast cancer and sentinel node metastasis, but in 60% of the cases there is no further axillary neoplastic involvement, so this invasive intervention represents an overtreatment. The purpose of the study is to identify patients with low risk of additional nodal metastases, to omit ALND. Methods The MSKCC Additional nodal metastasis nomogram was applied on a sample of 175 patients with invasive breast cancer who underwent ALND after detection of macrometastasis with the extemporaneous examination of the sentinel lymph node. Patients were classified as "low risk" when the result of the nomogram was ≤50%. Sensitivity, specificity, positive and negative predictive values and AUC (Area Under Curve) of the ROC curve of the nomogram were then calculated. Results A cut-off by 50% yielded 92.3% sensitivity, 81,4% specificity, 80% positive predictive value and 92.9% negative predictive value. The ROC curve AUC in these patients was 0.885. Conclusions The MSKCC nomogram has proven to be an effective tool in estimating the axillary lymph node status and it can potentially be used to better select the patients with sentinel node macrometastasis who can actually benefit from ALND.

Sentinel lymph node biopsy (SLNB) is a minimally invasive technique to stage the axillary lymph node status. The burden of nodal metastasis is of great concern, as the clinical relevance and therapeutic implications of pN1mi and pN0(i+) in the sentinel lymph node (SLN) remain a matter of debate.We examined the pathological features of 901 patients above the age of 65 presenting with clinical T1-T2 N0M0 breast tumours (3 cm), detecting tumours related to llary non-sentinel node (NSN) metastases when the SLN was minimally involved.A total of 270 patients underwent complete axillary lymph node dissection (cALND) after their SLNB specimen tested positive for macrometastasis, micrometastasis and isolated tumour cells (ITCs). Seventy-six patients were diagnosed with micrometastatic disease pN1mi (27.5%), whilst ITCs (pN0i+) were detected in seven patients (2.5%). NSNs were found to be involved in two patients (2.6%) with micrometastases at the SLN. No further metastatic disease was detected in NSNs when the SLN contained ITCs. At a median follow-up period of 5.8 years, no axillary recurrence was observed among pN1mi and pN0(i+) patients. Lobular histotype, multicentricity and lymphovascular invasion were found to be associated with NSN involvement.The results from our case series are supported by IBCSG 23-01 level 1 evidence, which demonstrated a local recurrence rate of 1% in 'minimally involved not-surgical treated axilla'.Based on current evidence, we spare well-informed and consenting patients from further axillary surgery when the SLN is minimally involved in early breast cancer within an agreed protocol, whilst scheduling adjuvant treatment based on the patients' primary tumour characteristics.

Background. Publication of the results of the randomised ACOSOG Z0011 trial concerning the possibilities of conservative treatment of breast cancer patients with macrometastasis in the sentinel lymph node (SLN) increased the interest in this therapeutic option. The objective of the study was to assess the practical effects of the implementation of conclusions from the aforementioned study as well as clinical consequences of abandoning intraoperative verification of sentinel lymph nodes resected during the surgical procedure. Material and methods. A prospective analysis was made for 567 breast cancer patients subjected to sentinel node biopsy in the period 1 January to 31 October 2014. In the case of the group undergoing breast conserving treatment (BCT), routine intraoperative assessment of SLN was abandoned. The decision regarding potential radicalisation of the surgical procedure was delayed until final histopathological results were obtained. The results were compared with data from the period preceding the implementation of changes. Results. BCT was used in 73.4% of study subjects while breast amputation was performed in the remaining patients. Presence of metastatic lesions within the SLNs was detected in 23.5% of patients. In 31.8% of patients with SLN metastases, radicalisation of the surgery was abandoned versus 18.3% in the control group, 22.2% versus 5.1% in case of macrometastases; 28.0% versus 6.5% in patients undergoing BCT. These are significant results, p < 0.05). The percentage of patients subjected to reoperation was 6.9% versus 3.6% in the control group. Conclusions. Postponing the decision regarding the potential radicalisation of surgical treatment until the receipt of the final result of the histopathological sentinel node assessment may facilitate the choice of further treatment. Abandonment of routine intraoperative assessment of SLN allowed for a statistically significant increase in the percentage of follow-up axillary lymph node resection being abandoned. At the same time, no significant increase in the rate of reoperations was observed.

Introduction Patients with four or more axillary lymph node metastases have benefited from postmastectomy radiotherapy to the supraclavicular region. However, when metastatic sentinel nodes (SNs) are present, information regarding the total number of node metastases cannot be obtained if axillary lymph node dissection (ALND) is omitted from the treatment protocol. It is important to determine the indication for additional chemotherapy in ER-positive and HER2-negative breast cancer patients. We investigated the predictive factors for the occurrence of four or more metastases in patients with ER-positive and HER2-negative breast cancer in the presence of macrometastasis in the SNs. Methods We reviewed 83 patients with ER-positive and HER2-negative breast cancer, who had macrometastasis in the SN and had undergone ALND. The clinicopathological findings and prognosis between patients with pN1 disease and those with pN2 disease were also compared. Results Nineteen percent of patients had pN2–3 disease. The predictive factor for poor prognosis in these patients was the presence of pN2–3 disease. The independent predictive factors for pN2–3 disease were the T stage and the ratio of the number positive SNs to the number of removed SNs (SN ratio). Patients with both T2 tumors and a high SN ratio had a 50% risk of having pN2–3 disease. Conclusion The presence of four or more metastases was found to be the strongest prognostic factor in ER-positive and HER2-negative breast cancer patients with macrometastasis in the SN. The T stage and SN ratio determined before surgery or during surgery were useful in predicting pN2–3 disease in these patients.

Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.

Objective: Intraoperative evaluation of sentinel lymph nodes (SLNs) for patients with breast cancer is widely performed with frozen section (FS), cytology, or a combination of both. Touch imprint cytology (TIC) reportedly has an equivalent sensitivity to FS. We studied its diagnostic utility to detect SLN metastases. Materials and Methods: Cases of 367 patients with breast cancer who underwent intraoperative valuation of SLNs (507 LNs) were evaluated. All FS and corresponding TIC slides of SLNs of each case were reviewed microscopically for the presence of metastases of any size. If present, the metastatic focus was measured on the FS. Results: Of these 507 SLNs, 82 LNs (16.2%) from 69 women were found to have metastases in the FS and consisted of 5 LNs of isolated tumor cells, 15 of micrometastasis, and 62 of macrometastasis. TIC identified metastases in 69 of these 82 SLNs (sensitivity: 84.1%, specificity: 100%, and accuracy: 97.4%). All macrometastases could be detected by TIC, whereas TIC identified approximately 50% of micrometastases and none of isolated tumor cells. The size detection limit of metastatic foci, defined as the smallest dimension of metastasis detected without false negatives, was 2 mm. The smallest metastatic focus identified was 0.8 mm. Conclusions: TIC of SLNs is of great use given its negative predictive value of 100% for identification of macrometastasis in our study. For intraoperative evaluation of SLNs, based on our data, a practical two-step approach is proposed: SLN evaluation should be initially performed by TIC and then proceed to FS histological analysis only when cytologically positive to determine the size of metastatic focus.

OBJECTIVE: To assess the rates and distribution of first recurrence in patients with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic dissection at surgical staging. METHODS: We retrospectively selected all (n=207) stage IIIC1 patients treated at a single institution from 5/1993–1/2017. Sites of first recurrence were identified, disease-free (DFS) and overall survival (OS) calculated, multivariate logistic regression performed to identify factors associated with recurrence. RESULTS: Three-year DFS and OS were 66.5% and 85.7%, respectively. The most common histology was endometroid (64.2%). Three-year DFS was 81% (SE+/−3.8%) endometrioid vs. 39.5% (SE+/−6.6%) non-endometrioid (P

Objective Lymphadenectomy in papillary thyroid carcinoma (PTC) is controversial. It is indicated whenever metastases have been proven before or during surgery and as a prophylactic treatment in high-risk patients. However, 30–50% of cN0 patients become pN1 postoperatively. In PTC, selective-sentinel-lymph-node-biopsy (SLNB) with conventional intraoperative analysis is 8% false negative. One-step nucleic acid amplification (OSNA) is a molecular technique which allows real-time detection of mRNA encoding for cytokeratin 19. OSNA has been introduced in intraoperative analysis of several tumors to reduce false-negative rates and distinguish micrometastasis from macrometastasis. Our objective was to evaluate the impact of the introduction of OSNA in the intraoperative evaluation of the sentinel node (SN) in PTC. Design We analyzed a series of 35 patients subjected to SLNB. Methods All the dissected nodes, SN and non-SN, were evaluated with OSNA and cytology. Results We obtained a total of 110 SN. SLNB proved positive in 14 patients (40%) with cytology and in 23 (65.7%) with OSNA (P P = 0002). The majority of patients with micrometastasis in SN showed only micrometastasis in lymphadenectomy. Conclusions The present study shows selective-sentinel-lymph-node-biopsy with one-step nucleic acid amplification technique to be feasible in papillary thyroid carcinoma. The quantitative nature of one-step nucleic acid amplification paves the way toward a more personalized surgical approach, limiting lymphadenectomy to patients with intraoperative evidence of macrometastasis in the sentinel node.

The aim of this study was to investigate preoperative factors associated with ductal carcinoma in situ (DCIS) upstaged to invasive ductal carcinoma (IDC) and sentinel lymph node (SLN) status in patients who underwent mastectomy for a preoperative diagnosis of DCIS. The medical records of 220 patients who underwent mastectomy for a preoperative diagnosis of DCIS were retrospectively reviewed. Fifty-one (22.6%) of 226 lesions were upgraded to IDC after mastectomy. Preoperative factors associated with upstaging to IDC included patient-reported signs and symptoms, a clinically palpable mass, ultrasound findings classified as category 4 or 5, the ultrasound appearance of a mass or widely distributed non-mass abnormality (NMA), and a high Ki67 index. The prevalence of SLN macrometastasis was 0.9%. IDC was diagnosed for 10.9% of lesions of a preoperative ultrasound category of 0–3, 13.0% of those with no mass or NMA detected by ultrasonography, and 14.1% of lesions preoperatively diagnosed by methods other than core needle biopsy (CNB). Of those lesions, none was associated with SLN metastasis. Routinely performing SLN biopsy for patients undergoing mastectomy for a preoperative diagnosis of DCIS is overtreatment, because the prevalence of SLN metastasis was low. SLN biopsy can be omitted for most patients. In particular, we suggest omitting SLN biopsy for patients who have lesions of ultrasound category 0–3, who have neither a mass nor NMA detected by ultrasound, or whose initial diagnosis was made based on a specimen obtained by methods other than CNB.