Search

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.

Objectives We compared the traditional ultrastaging (SU) with the one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis in women with apparent early stage endometrial carcinoma (EC). Methods All women were surgically staged including SLN mapping. Nodes were cut perpendicular to the long axis and two adjacent 5 mm sections were cut at each of 2 levels 50 mm apart, and one slide was stained with H&E and the other with immunohistochemistry using the AE1/AE3 anticytokeratin antibody, and one negative control slide for a total of five slides per block. For OSNA analysis, the 2mm sections of the SLN were homogenized to form a lysate that was centrifuged and inserted into the RD100i instrument where for the isothermal amplification of CK19 mRNA. Results Totally 409 patients were included in the analysis (183 OSNA, 226 SU). Overall, 3521 lymph nodes were removed, of those 871 SLN’s (24.7%) were identified (381 OSNA, 490 SU). Sixty patients had metastasis on SLN’s (26 OSNA, 34 SU). Macrometastasis, micrometastases, and ITC were 25.7%, 68.6% and 5.7% for OSNA; 48.1%, 36.5% and 15.4% for SU (p = 0.015). ITC alone were recorded in 7 women (2 OSNA, 5 SU). Conclusions The OSNA assay detected a higher rate of micrometastasis and a lower rate macrometastasis and ITC compared to SU. The clinical and prognostic impact of ITC is still controversial. Further studies are needed to clarify the clinical impact of the OSNA assessment technique and the prognostic impact of ITC in patients with stage I EC.

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).

La afectación ganglionar se ha considerado hasta el momento un factor relevante para la supervivencia, estadiaje y tipo de tratamiento de las pacientes diagnosticadas de cáncer de mama. Se define al ganglio centinela (GC) como el primer ganglio de una cadena linfática que recibe el flujo linfático desde el tumor primario. Si este ganglio no contiene células tumorales es poco probable que el resto de ganglios axilares presenten enfermedad metastásica (1). La identificación del ganglio centinela puede sustituir a la linfadenectomía axilar para el estudio de extensión regional en el cáncer de mama, evitando su morbilidad asociada (2). Hoy en día, está aceptada la realización de la biopsia selectiva del ganglio centinela en aquellos casos de carcinomas infiltrantes T1, T2 y T3 (siempre que la axila sea clínica, ecográfica y patológicamente negativa) y presente menos de 3 ganglios centinela positivos. También se realiza en los casos de carcinoma intraductal con indicación de mastectomía o alto riesgo para infiltración (≥ 3cm, tumor palpable, alto grado histológico o comedonecrosis) (3) (4) (5) (6) (7) (8). La BSGC está contraindicada en el caso de la verificación preoperatoria de afectación ganglionar mediante pruebas de imagen y confirmada con biopsia, en el carcinoma inflamatorio, si ha recibido radioterapia axilar previa a dosis de 50 Gy y en el carcinoma localmente avanzado que presente afectación ganglionar con extensión extranodal (3)(4). Se define como ganglio positivo aquél que presenta células tumorales metastásicas en el estudio histológico o más de 100 copias de mARN-CK19 en el estudio OSNA. Se clasifican como macrometástasis aquellos con más de 2 mm de diámetro sobre la laminilla o equivalencia en número de copias de ARNm-CK19 mayor o igual a 5000 copias (9) (10). Está demostrado que la existencia de células tumorales aisladas y las micrometástasis no precisan la realización de linfadenectomía axilar. Sin embargo, en la actualidad todavía existen controversias respecto a la indicación de linfadenectomía axilar respecto a los casos de macrometástasis con baja carga tumoral (igual o menor de 10000 - 15000 copias) o perfil de bajo riesgo (hasta dos GC metastásicos, estatus post-menopáusico, tamaño menor de 3 cm, grado histológico 1 o 2, receptores hormonales positivos, Her2 negativo, Ki67 ≤14%, cirugía conservadora). En estos casos, se podría obviar la linfadenectomía incorporando el tratamiento adyuvante con radioterapia (3)(11)(12). Todavía constituye indicación habitual de linfadenectomía axilar la carga tumoral mayor a 10.000-15.000 copias o las macrometástasis en aquellos casos que no son de “bajo riesgo” (3). Por otro lado, pueden existir casos con cánceres pequeños y axila clínicamente negativa, candidatos a cirugía conservadora de mama con radioterapia adyuvante y valoración preoperatoria negativa por imagen de la axila en los que podría obviarse la realización de la biopsia selectiva del ganglio centinela siempre y cuando las pacientes fueran sometidas a un adecuado seguimiento. Las tendencias actuales se dirigen hacia una cirugía cada vez menos invasiva, evitando la linfadenectomía axilar en un número cada vez mayor de pacientes, gracias a la realización de la biopsia selectiva del ganglio centinela. Los objetivos de este trabajo son identificar variables que puedan modificar la actitud terapéutica en el cáncer de mama, tanto en los casos de tumores avanzados con diagnóstico de macrometástasis en la biopsia selectiva del ganglio centinela, como en el caso de tumores de bajo grado o con características especiales, en los que podría obviarse el estudio del ganglio centinela. También son objetivos: analizar las tasas de recidiva y supervivencia según su estadio y diagnóstico del ganglio centinela y estudiar las posibles asociaciones de los factores pronósticos considerados con las recidivas y supervivencia. Se trata de un estudio retrospectivo consecutivo observacional multicéntrico de las pacientes diagnosticadas e intervenidas de cáncer de mama entre los años 2000 y 2014 en el hospital de la Ribera. Excluimos las pacientes con neoplasia de mama previa ipsilateral, metástásicas de inicio, con quimioterapia neoadyuvante, con historia clínica incompleta o intervenidas en otros hospitales. Estudiamos los antecedentes, los métodos diagnósticos de imagen e histológicos utilizados, el tipo de tumor, así como su estadio, el tipo de intervención quirúrgica, el ganglio centinela, el tratamiento adyuvante que ha recibido la paciente y el seguimiento hasta el 15 de marzo de 2018. Revisamos una población de 1641 pacientes intervenidas de cáncer de mama sin quimioterapia neoadyuvante, 1135 de las cuales tienen realizado GC. Encontramos un 14.85% de fallecidas y/o recidivas al finalizar el seguimiento, una supervivencia libre de enfermedad del 90.03% de las pacientes a los 5 años y del 82.36% a los 10 años y un 12.16% de recidivas. El estudio de Shigemizu muestra unas tasas de supervivencia libre de enfermedad a 11 años similares (76.5%) (13). De los 1135 casos en los que se ha realizado GC el 11.85% presentaron un GC afecto por macrometástasis y el 79.54% obtuvieron un GC negativo. Nuestra muestra presenta un mayor porcentaje de GCs negativos que el ensayo clínico NSABP B-32 (71.1%) (14), objetiva resultados similares a Dengel et al (82.4%) (15) y algo menores que Toshikawa et al (85%) (16) e Ibrahim-Zada et al (87%) (17). En nuestro análisis estadístico, aumenta el riesgo de GC positivo un 5.2% por cada incremento de tamaño tumoral de un mm y aparece 2.80 veces más riesgo si existe invasión linfovascular. Factores de riesgo similares muestran los estudios de Tapia (18) y de Zheng (19). Los tumores de estirpe triple negativo presentan menor riesgo de afectación ganglionar, factor ya comentado por Marazzo (20), Vane (21) y Ozbas (22). La proporción de pacientes con ganglios afectos adicionales a los ganglios centinela se incrementa de forma más acusada por encima de valores de OSNA de 12000 y la proporción de tumores con estos valores aumenta en función del tamaño tumoral, alcanzando el máximo en el tamaño a partir de 5 cm. Hay estudios que muestran un corte de TTL similar (10000 copias en el análisis de Piñero-Madrona et al (23) y 15000 en el de Fung et al (24)). Otros sin embargo proponen un corte mayor, como Peg et al (25) y el estudio NEOVATTL (26) que establecen el corte en 25000, Kubota en 54000 (27), Ohi en 100000 (28), Espinosa-Bravo en 120000 (29) y Nabais en 190000 (30). El 14.9% de los tumores con histología en biopsia previa in situ e infiltrante en la definitiva, tenían el ganglio centinela positivo, datos similares al estudio de Sakr (31) y al de Camp (32). Los tumores con ganglio centinela positivo tuvieron en todos los casos un tamaño de 11 mm o superior. Francis et al (33) y Miyake et al (34) establecen el corte en 20 mm y Huo en 15 mm (35). En cuanto a la mortalidad específica se produce un riesgo 3.33 veces superior en tumores con macrometástasis y 3.77 veces superior en tumores con GC no realizado, respecto a GC negativo y se incrementa el riesgo un 5.5% por cada ganglio positivo y un 88% en tumores con invasión linfovascular. Los estudios de Tonelloto (36) y Saadatmand (37) plasman este descenso de supervivencia. Los metanálisis de Gujam (38) y de Zhang (39) demuestran que la invasión linfovascular predice un pronóstico más pobre. La supervivencia libre de enfermedad (SLE) empeora un 3.7% por cada ganglio positivo y 3.14 veces más si se realiza linfadenectomía axilar. Los estudios de Ozcan (40) y Joo (41) y el ensayo ACOSOG Z0011 (11)(12) exponen que la omisión de la linfadenectomía en pacientes con afectación axilar ganglionar limitada no muestra una peor supervivencia. También empeora la SLE a partir de los 20 mm y en tumores con Ki67 alto, como objetiva en estudio de Inwald et al (42). Según los datos de nuestro estudio podemos exponer que los tumores menores de 5 cm, sin invasión linfovascular, cuyo análisis de GC por OSNA sea menor de 12000 copias tienen baja posibilidad de presentar ganglios adicionales afectos y, por tanto, pueden beneficiarse de la no realización de un vaciamiento axilar, ya que no mejora la supervivencia libre de enfermedad. La administración de quimioterapia neoadyuvante en pacientes con afectación ganglionar tampoco mejora la misma. Deberíamos también considerar la necesidad de la realización del ganglio centinela en las pacientes con bajo riesgo de afectación axilar (CDIS, carcinoma ductal y carcinoma lobulillar infiltrante puro de 10 mm o menos). Bibliografía: 1. Acea Nebril B, Candia Bouso B, Sobrido Prieto M, Ramos Boyero M. Biopsia del ganglio centinela en enfermas con cancer de mama. Estudio de evaluación técnica desde los criterios de la medicina basada en la evidencia. Asociación Española de Cirujanos; 2003. [consultado 31 de marzo de 2019] Disponible en: http://www.breastsurgeonsweb.com/wp-content/uploads/downloads/2012/10/516.pdf 2. Fougo JL, Dinis-Ribeiro M, Araújo C, Dias T, Reis P, Giesteira L, et al. Impacto de la linfadenectomía sobre la recurrencia axilar y la morbilidad del miembro superior en pacientes con cáncer de mama y ganglio centinela negativo. Estudio prospectivo aleatorizado. Cirugía Española. Mayo de 2011;89(5):307-16. 3. Bernet L, Piñero A, Vidal-Sicart S, Peg V, Giménez J, Algara M, et al. Consenso sobre la biopsia selectiva del ganglio centinela en el cáncer de mama. Revisión 2013 de la Sociedad Española de Senología y Patología Mamaria. Revista Española de Patología. Enero de 2014;47(1):22-32. 4. Manca G, Rubello D, Tardelli E, Giammarile F, Mazzarri S, Boni G, et al. Sentinel Lymph Node Biopsy in Breast Cancer: Indications, Contraindications, and Controversies. Clinical Nuclear Medicine. Febrero de 2016;41(2):126-33. 5. Giammarile F, Alazraki N, Aarsvold JN, Audisio RA, Glass E, Grant SF, et al. The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer. European Journal of Nuclear Medicine and Molecular Imaging. Diciembre de 2013;40(12):1932-47. 6. Carlson GW. Management of Axillary Lymph Node Metastasis in Breast Cancer: Making Progress. JAMA. 9 de febrero de 2011;305(6):606-7. 7. Randomized Trial Comparing Axillary Clearance Versus No Axillary Clearance in Older Patients With Breast Cancer: First Results of International Breast Cancer Study Group Trial 10-93. Journal of Clinical Oncology. 20 de enero de 2006;24(3):337-44. 8. Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. Mayo de 2014;32(13):1365-83. 9. The Bay Area SLN Study, Kohrt HE, Olshen RA, Bermas HR, Goodson WH, Wood DJ, et al. New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients. BMC Cancer [Internet]. Diciembre de 2008 [citado 27 de enero de 2019];8(1). Disponible en: http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-66 10. López-Zambrano M, Ruiz N, Soler MT, Pla MJ, Quetglas C, Pérez-Martín J, et al. Estudio comparativo entre el método One step nucleic acid amplification y el método convencional en la estadificación en cáncer de mama: un aumento en la detección de micrometástasis. Revista de Senología y Patología Mamaria. Octubre de 2016;29(4):143-9. 11. Acea B, Calvo Martínez L, Antolín Novoa S, Albaina Latorre L, Juaneda Magdalena M, Santiago Freijanes P, et al. Propuesta de una nueva estrategia terapéutica multidisciplinar en la mujer con cáncer de mama y afectación del ganglio centinela. Cirugía Española. Diciembre de 2012;90(10):626-33. 12. Giuliano AE, Ballman K, McCall L, Beitsch P, Whitworth PW, Blumencranz P, et al. Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Annals of Surgery. Septiembre de 2016;264(3):413-20. 13. Shigemizu D, Iwase T, Yoshimoto M, Suzuki Y, Miya F, Boroevich KA, et al. The prediction models for postoperative overall survival and disease-free survival in patients with breast cancer. Cancer Medicine. Julio de 2017;6(7):1627-38. 14. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. The Lancet Oncology. Octubre de 2010;11(10):927-33. 15. Dengel LT, Van Zee KJ, King TA, Stempel M, Cody HS, El-Tamer M, et al. Axillary Dissection Can Be Avoided in the Majority of Clinically Node-Negative Patients Undergoing Breast-Conserving Therapy. Annals of Surgical Oncology. Enero de 2014;21(1):22-7. 16. Toshikawa C, Koyama Y, Nagahashi M, Tatsuda K, Moro K, Tsuchida J, et al. Predictive Factors for Non-Sentinel Lymph Node Metastasis in the Case of Positive Sentinel Lymph Node Metastasis in Two or Fewer Nodes in Breast Cancer. Journal of Clinical Medicine Research. 2015;7(8):620-6. 17. Ibrahim-Zada I, Grant CS, Glazebrook KN, Boughey JC. Preoperative Axillary Ultrasound in Breast Cancer: Safely Avoiding Frozen Section of Sentinel Lymph Nodes in Breast-Conserving Surgery. Journal of the American College of Surgeons. Julio de 2013;217(1):7-15. 18. Tapia G, Ying V, Di Re A, Stellin A, Cai TY, Warrier S. Predicting non‐sentinel lymph node metastasis in Australian breast cancer patients: are the nomograms still useful in the post‐Z0011 era? ANZ Journal of Surgery [Internet]. 7 de mayo de 2019 [citado 22 de mayo de 2019]; Disponible en: https://onlinelibrary.wiley.com/doi/abs/10.1111/ans.15173 19. Zheng J, Cai S, Song H, Wang Y, Han X, Wu H, et al. Positive non-sentinel axillary lymph nodes in breast cancer with 1-2 sentinel lymph node metastases: Medicine. Noviembre de 2018;97(44):e13015. 20. Marrazzo A, Boscaino G, Marrazzo E, Taormina P, Toesca A. Breast cancer subtypes can be determinant in the decision making process to avoid surgical axillary staging: A retrospective cohort study. International Journal of Surgery. Septiembre de 2015;21:156-61. 21. Vane MLG, van Nijnatten TJA, Nelemans PJ, Lobbes MBI, van Roozendaal LM, Kooreman LFS, et al. Does the subtype of breast cancer affect the diagnostic performance of axillary ultrasound for nodal staging in breast cancer patients? European Journal of Surgical Oncology. Abril de 2019;45(4):573-7. 22. Ozbas S, Ozmen V, Igci A, Muslumanoglu M, Ozcinar B, Balkan M, et al. Predicting the Likelihood of Nonsentinel Lymph Node Metastases in Triple Negative Breast Cancer Patients With a Positive Sentinel Lymph Node: Turkish Federation of Breast Disease Associations Protocol MF09-01. Clinical Breast Cancer. Febrero de 2012;12(1):63-7. 23. Piñero-Madrona A, Ruiz-Merino G, Bernet L, Miguel-Martínez B, Vicente-García F, Viguri-Díaz MA, et al. Tumoral load quantification of positive sentinel lymph nodes in breast cancer to predict more than two involved nodes. The Breast. Diciembre de 2014;23(6):859-64. 24. Fung V, Kohlhardt S, Vergani P, Zardin GJ, Williams NR. Intraoperative prediction of the two axillary lymph node macrometastases threshold in patients with breast cancer using a one-step nucleic acid cytokeratin-19 amplification assay. Molecular and Clinical Oncology. noviembre de 2017;7(5):755-62. 25. Peg V, Sansano I, Vieites B, Bernet L, Cano R, Córdoba A, et al. Role of total tumour load of sentinel lymph node on survival in early breast cancer patients. The Breast. Junio de 2017;33:8-13. 26. Vieites B, López MA, Martín MD, López L, Rezola R, Sancho M, et al. Carga tumoral total: factor predictivo y pronóstico en cáncer de mama tras terapia neoadyuvante- estudio NEOVATTL. 37º Congreso SESPM; 2018; Cádiz. 27. Kubota M, Komoike Y, Hamada M, Shinzaki W, Azumi T, Hashimoto Y, et al. One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis. Molecular and Clinical Oncology. Febrero de 2016;4(2):173-8. 28. Ohi Y, Umekita Y, Sagara Y, Rai Y, Yotsumoto D, Matsukata A, et al. Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer. British Journal of Cancer. Octubre de 2012;107(8):1239-43. 29. Espinosa-Bravo M, Sansano I, Pérez-Hoyos S, Ramos M, Sancho M, Xercavins J, et al. Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay. European Journal of Surgical Oncology (EJSO). Julio de 2013;39(7):766-73. 30. Nabais C, Figueiredo J, Lopes P, Martins M, Araújo A. Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer. The Breast. Abril de 2017;32:33-6. 31. Sakr R, Antoine M, Barranger E, Dubernard G, Salem C, Daraï E, et al. Value of Sentinel Lymph Node Biopsy in Breast Ductal Carcinoma in Situ Upstaged to Invasive Carcinoma. The Breast Journal. Enero de 2008;14(1):55-60. 32. Camp R, Feezor R, Kasraeian A, Cendan J, Schell S, Wilkinson E, et al. Sentinel Lymph Node Biopsy for Ductal Carcinoma in Situ: An Evolving Approach at the University of Florida. The Breast Journal. Noviembre de 2005;11(6):394-7. 33. Francis AM, Haugen CE, Grimes LM, Crow JR, Yi M, Mittendorf EA, et al. Is Sentinel Lymph Node Dissection Warranted for Patients with a Diagnosis of Ductal Carcinoma In Situ? Annals of Surgical Oncology. Diciembre de 2015;22(13):4270-9. 34. Miyake T, Shimazu K, Ohashi H, Taguchi T, Ueda S, Nakayama T, et al. Indication for sentinel lymph node biopsy for breast cancer when core biopsy shows ductal carcinoma in situ. The American Journal of Surgery. Julio de 2011;202(1):59-65. 35. Huo L, Sneige N, Hunt KK, Albarracin CT, Lopez A, Resetkova E. Predictors of invasion in patients with core-needle biopsy-diagnosed ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy in ductal carcinoma in situ. Cancer. 15 de octubre de 2006;107(8):1760-8. 36. Department of Surgical Oncology, Mastology Service, Hospital do Câncer III, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brasil, Tonellotto F, Bergmann A, Department of Clinical Research, Research Center, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brasil, Abrahao K de S, Department of Clinical Research, Research Center, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brasil, et al. Impact of Number of Positive Lymph Nodes and Lymph Node Ratio on Survival of Women with Node-Positive Breast Cancer. European Journal of Breast Health. 4 de abril de 2019;15(2):76-84. 37. Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MMA. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173 797 patients. BMJ. 6 de octubre de 2015;h4901. 38. Zhang S, Zhang D, Gong M, Wen L, Liao C, Zou L. High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer. BMC Cancer [Internet]. diciembre de 2017 [citado 26 de mayo de 2019];17(1). Disponible en: http://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3338-x 39. Gujam FJA, Going JJ, Edwards J, Mohammed ZMA, McMillan DC. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer. Critical Reviews in Oncology/Hematology. Febrero de 2014;89(2):231-41. 40. Ozcan LC, Giuliano AE. Is Axillary Lymph Node Dissection Necessary After a Positive Sentinel Lymph Node Biopsy? Advances in Surgery. Septiembre de 2017;51(1):165-78. 41. Joo JH, Kim SS, Son BH, Ahn SD, Jung JH, Choi EK, et al. Axillary Lymph Node Dissection Does Not Improve Post-mastectomy Overall or Disease-Free Survival among Breast Cancer Patients with 1–3 Positive Nodes. Cancer Research and Treatment [Internet]. 16 de octubre de 2018 [citado 26 de mayo de 2019]; Disponible en: http://www.e-crt.org/journal/view.php?doi=10.4143/crt.2018.438 42. Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Research and Treatment. Junio de 2013;139(2):539-52.

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.

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.

Sentinel lymph-node biopsy has reduced the need for extensive axillary surgery for staging. It still exposes women to associated morbidity. Risk models that use clinical and pathology information of the primary tumour to predict sentinel lymph-node metastasis may allow further improvements in care. This study assessed the performance of four published risk models for predicting sentinel lymph-node metastasis in Australian women with early breast cancer; including one model developed in an Australian population.The Sentinel Node Biopsy Versus Axillary Clearance (SNAC) trial dataset was used to assess model discrimination by calculating the area under the receiver-operating-characteristic curve (AUC) and the false-negative rate for sentinel lymph-node metastasis using model-predicted risk cut-points of 10%, 20%, 30%, and calibration using Hosmer-Lemeshow tests and calibration plots.The sentinel node was positive in 248 of 982 (25.2%) women (158 macrometastasis, 90 micrometastasis). The AUCs of risk models ranged from 0.70 to 0.74 for prediction of any sentinel-node metastasis; 0.72 to 0.75 for macrometastasis. Calibration was poor for the three models developed outside of Australia (lack-of-fit statistics, P 0.001). For women with a model-predicted risk of sentinel lymph-node metastasis ≤10%, observed risk was 0-13% (three models10%), false-negative rate 0-9%; 1-17% of women were classified in this range.All four models showed good discrimination for predicting sentinel lymph-node metastasis, in particular for macrometastasis. With further development such risk models could have a role in the provision of reassurance to low risk women with normal nodes sonographicaally for whom no axillary surgery is contemplated.

Background Recent clinical trials have shown that axillary lymph node dissection can be omitted even with positive sentinel nodes (SN) unless the patient undergoes total mastectomy without irradiation. The aim of our study was to identify predictive factors for non-SN metastasis among patients with solitary or multiple breast cancer treated with total mastectomy. Patients and Methods Clinically node-negative breast cancer patients with pathologically node-positive disease treated with total mastectomy and axillary dissection after SN biopsy were retrospectively analyzed. Significant pathologic predictive factors for positive non-SN metastasis were also examined. Results There were 47 multiple and 143 solitary breast cancer patients. Pathologic diagnosis demonstrated that smaller invasion size but larger tumor size, including adjacent noninvasive cancer, was observed in multiple breast cancer. The number of involved SNs and the rate of non-SN metastasis were similar between the multiple and solitary groups. Regarding predictive factors for non-SN metastasis, lymphatic invasion and SN macrometastasis were significant factors in the solitary group, and pathologic invasion size > 2 cm was the only significant factor in the multiple group. Conclusion Larger pathologic invasion size was important for predicting non-SN metastasis in multiple breast cancer.

Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P

Merkel cell carcinoma is an aggressive neuroendocrine tumor with high rates of local recurrence, micro- and macrometastasis. Its poor prognosis underscores the importance of determining effective treatment protocols. However, given its rarity, there is a paucity of prospective randomized trials to guide evidence-based management. Current guidelines are largely based on retrospective reviews and expert consensus opinion. In general, treatment centers on addressing the primary tumor first, followed by management of nodal and/or metastatic disease. This review discusses therapeutic options by disease stage and highlights where questions remain to be answered.

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups.

Sentinel lymph node biopsy has been started in 1990s and has become one of the standard diagnostic procedures used to treat patients with early breast cancer in this century. In Japan, for the microscopic diagnosis of metastasis to sentinel lymph nodes, intraoperative frozen section diagnosis is widely used in combination with subsequent permanent section diagnosis of the residual specimens. Metastatic foci to sentinel lymph nodes have been classified into macrometastasis, micrometastasis, and isolated tumor cells in 2002, and the definition of isolated tumor cells was modified in 2010. Clinical significance of occult sentinel lymph node metastases, being mostly composed of micrometastasis and isolated tumor cells, has been clarified in terms of predictive factors for non-sentinel lymph node metastasis and patient prognosis by large-scale retrospective studies and prospective randomized clinical trials. In the present review, clinical implications of micrometastases and isolated tumor cells in sentinel lymph nodes and the methods for pathological examination of SLN metastases employed in these studies were overviewed.

Background Z0011 study suggests patients with minimal disease do not require axillary clearance. Exclusions include T3 tumours, mastectomy or neoadjuvant treatment. This study assessed the utility of pre-operative US-guided core biopsy of axillary nodes and its correlation with nodal macrometastases. Methods 247 women with breast cancer outside Z0011 criteria were reviewed retrospectively. Sensitivity and specificity of pre-operative axillary ultrasound and core biopsy compared to final histology was assessed by contingency tables. Results 75/247 patients had macrometastases. Ultrasound-axilla was 72% sensitive and 77% specific in predicting macrometastasis. The positive (PPV) and negative predictive value (NPV) was 58% and 86.4% respectively. Core-biopsy of axilla node, was 92.6% sensitive and 66.7% specific in detecting macrometastasis. PPV and NPV 79.4% and 86.7% respectively. Conclusion Positive pre-operative ultrasound-guided core biopsy accurately predicts macroscopic involvement of axillary nodes. Selected patients outside Z0011 parameters can proceed to axillary clearance without sentinel node biopsy or risking overtreatment.

Purpose The aim of this study was to evaluate the correlation between central lymph node (CLN) metastasis and clinicopathologic characteristics of papillary thyroid cancer (PTC). In addition, we investigated the incidence and risk factors for contralateral CLN metastasis in unilateral PTC. This study suggests the appropriate surgical extent for CLN dissection. Methods A prospective study of 500 patients with PTC who underwent total thyroidectomy and prophylactic bilateral CLN dissection was conducted. Results Of 500 patients, 255 had CLN metastases. The rate of CLN metastasis was considerably higher in cases of younger patients (

Aim To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. Materials and methods Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. Results Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection was 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24–75). Conclusion Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up.

Objective The aim of the present study was to investigate the association between non sentinel lymph node metastasis (NSLNM) and clinicopathological factors, particularly in the case of sentinel lymph node (SLN) metastasis in one or two, in clinically node negative patients with breast cancer. Methods Between 10/2010 and 10/2014, 350 sentinel lymph node biopsy (SLNB) were performed in patients with histologically proven primary breast cancer in our clinic. The data collection includes the following characteristics: age, pathological tumor size, histological type, histological grade, lymphovascular invasion (LVI), number of positive SLN, size of the SLN metastasis (macrometastasis, micrometastasis, isolated tumor cells), multifocality (MF), extracapsuler invasion (ECI) of the SLN, the estrogen receptor (ER) status, the progesterone receptor (PR) status and the Her 2 receptor status, Ki 67 reseptor status. Data were collected retrospectively and then analyzed. Results A successful SLN biopsy were performed in 345 (98.5%) cases. SLN metastases were detected in 110 (31.8%) cases. These patients then underwent axillary dissection; among these patients, 101 (91.8%) had only one to two positive SLNs. Of the 101 patients with positive SLN biopsies, 32 (31.6%) had metastases in the NSLNs. Univariate and multivariate analysis showed that lymphovascular invasion, extracapsular invasion (ECI), Her-2 receptor positive, and Ki-67 > 14% were related to NSLNM (p Conclusion The predicting factors of NSLNM were LVI, ECI, Ki-67 level, Her-2 reseptor positive and but should be further validated in our institutions, different institutions and different patient groups prospectively.

Background One-step nucleic acid amplification (OSNA) assay is a molecular diagnostic method for intraoperative detection of lymph node metastasis by amplifying cytokeratin 19 mRNA. We aim to further evaluate the performance of OSNA assay for the intraoperative diagnosis of sentinel lymph node metastasis in breast cancer. Methods PubMed, Cochrane Library, Web of Science databases were searched to retrieve related literature published up until December 2017. This meta-analysis was performed using a random-effects model. Risks of bias and quality assessments of included studies were evaluated and subgroup analysis was performed. Results Nineteen studies were included in this meta-analysis. For overall metastasis, the pooled sensitivity, specificity and area under the summary receiver-operating characteristic curve (AUC) were 0.90, 0.96 and 0.98, respectively. For macrometastasis, the pooled sensitivity, specificity and AUC were 0.85, 0.98 and 0.94, respectively. Conclusion OSNA assay is an accurate molecular diagnosis for intraoperative detection of sentinel lymph node macrometastasis in breast cancer.

Lymph node metastasis is a decisive factor for performing postoperative radiotherapy for oral squamous cell carcinoma (OSCC). However, whether OSCC patients with only micrometastasis need postoperative radiotherapy is unclear. In this study, OSCC patients (n = 311) with negative (n = 247), only micrometastasis (n = 44) and macrometastasis (n = 20) were detected and selected by HE staining. Micrometastasis was re-assessed using immunohistochemical staining of cytokeratin (CK) in HE-negative patients to find out the false negative cases. The results indicated that, among the negative lymph node cases (n = 247), the positive rate of CK was 4.94% (n = 12). Besides, the clinical features of the primary tumor in relation to the only micrometastatic status and the value of the postoperative radiotherapy on the only micrometastasis patients were evaluated. Patients with only micrometastasis had higher T stage and inferior worst pattern of invasion (WPOI) than patients without micrometastasis, but they had longer overall survival (OS), metastasis-free survival (MFS), and disease-free survival (DFS) than macrometastasis patients. However, the survival time of only micrometastasis patients with or without postoperative radiotherapy was comparable, even in patients with inferior WPOI. Radiotherapy, however, may only benefit patients with IV/V levels of micrometastasis. These data indicated that postoperative radiotherapy is dispensable for only micrometastasis OSCC patients.

Today, primary systemic therapy (PST) is an established and frequently used treatment in locally advanced and early breast cancer, which makes issues around sentinel lymph node biopsy (SLNB) in this context relevant. The question considered in this chapter is whether SLNB is an appropriate staging tool in the primary systemic therapy setting. Several prospective randomized studies have evaluated the feasibility and accuracy of SLNB in the era of PST. Current evidence indicates that SLNB can be used as the standard staging procedure in patients with initially (pretreatment) clinically node-negative breast cancer. In patients with initially node-positive disease (maybe converting to node negative during PST), SLNB should be scheduled after PST, even if the detection, accuracy and false-negative rate (FNR) are worse compared with SLNB before PST. After PST, at least three SLNs should be removed, and the use of dual-tracer mapping and immunohistochemistry are recommended in order to achieve satisfactory detection and FNRs. If SLNB yields micrometastases, macrometastasis or isolated tumour cells (ITCs) after PST, axillary dissection should follow. The issue of the optimal method for clinical or radiological axillary staging before surgery has to be determined in further studies.

The use of routine central compartment neck dissection surgery for papillary thyroid carcinoma (PTC) is controversial. Although macroscopic central neck lymph node metastasis (CNLN) in PTC is a poor prognostic factor correlated with increased loco-regional recurrence, the significance of microscopic metastasis to the central lymph nodes is not established. Herein, we aimed to assess the influence of the size of CNLN on disease recurrence among PTC patients. Data from 233 patients who underwent less than total thyroidectomy with CNLN dissection in 1989–1999 were retrospectively reviewed. The patients were assigned to three groups according to the central node metastasis: no metastasis (Group I), micrometastasis (

According to the current guidelines on treatment of breast cancer patients, identification of metastases in the sentinel lymph node (SLN (+)) is not an absolute indication for necessary axillary lymph node dissection (ALND). In our study, we present long-term outcomes of treatment among SLN(+) patients referred for conservative treatment, for example, no further ALND. A total of 3145 breast cancer patients subjected to sentinel lymph node biopsy (SLNB) between November 2008 and June 2015. SLN metastases were identified in 719 patients (22.9%). Locoregional recurrences and distant metastases as endpoints were distinquished. The mean follow-up time for patients after ALND was 36.2 months (6-74 months); 18.8 months (6-38 months) for patients with SLN macrometastases without ALND; and 34.0 months (6-74 months) for patients with micrometastases. Adjuvant ALND was performed in 626 of SLN(+) patients. Conservative treatment was applied in the remaining 93 cases. Among SLN(+) patients without adjuvant ALND, there was one case of recurrence (1.07%). In the group of patients without SLN, metastases recurrence was noted in 32 patients (1.32%). Among SLN(+) patients diagnosed with macrometastases, recurrence concerned 2.01% of analyzed cases (all subjected to ALND). Lack of radical surgical treatment in SLN(+) breast cancer patients did not lead to worsening long-term outcomes. In the occurrence of macrometastases to the sentinel lymph node, abandoning completion axillary lymph node dissection might be a reasonable option. However, it would require continuation of current research, preferably involving a clinical trial.