Value of total tumor load as a clinical and pathological factor in the prognosis of breast cancer patients receiving neoadjuvant treatment. Comparison of three populations with three different surgical approaches: NEOVATTL Pro 3 Study.

PURPOSE: This study aimed to compare the prognosis in terms of disease-free survival (DFS) in three populations of women with breast cancer (BC) treated with neoadjuvant systemic treatment (NAST) in which axillary lymph node dissection (ALND) was performed based on different total tumor load (TTL) thresholds in the sentinel nodes. METHODS: This was an observational, retrospective study carried out in three Spanish centers. Data from patients with infiltrating BC who underwent BC surgery after NAST and intraoperative sentinel lymph node biopsy (SLNB) performed by One Step Nucleic acid Amplification (OSNA) technique during 2017 and 2018 were analyzed. ALND was performed according to the protocol of each center, based on three different TTL cut-offs (TTL > 250, TTL > 5000, and TTL > 15,000 CK19-mRNA copies/µL for centers 1, 2, and 3, respectively). RESULTS: A total of 157 BC patients were included in the study. No significant differences in DFS were observed between centers (Hazard ratio [HR] center 2 vs 1: 0.77; p = 0.707; HR center 3 vs 1: 0.83; p = 0.799). Patients with ALND had a shorter DFS (HR 2.43; p = 0.136), albeit not statistically significant. Patients with a triple negative subtype had a worse prognosis than those with other molecular subtypes (HR 2.82; p = 0.056). CONCLUSION: No significant differences in DFS were observed between three centers with different surgical approaches to ALND based on different TTL cut-offs in patients with BC after NAST. These results suggest that restricting ALND to those patients with TTL ≥ 15,000 copies/µL is a reliable approximation, avoiding unnecessary morbidities caused by ALND.

Early and late results of open surgical and endovascular treatment of infrarenal abdominal aortic aneurysms, selected according to surgical risk.

BACKGROUND: Open surgical repair (OSR) and endovascular aneurysm repair (EVAR) surgery are alternative treatments for infrarenal abdominal aortic aneurysm (IRAAA). OBJECTIVES: To compare OSR and EVAR for the treatment of IRAAA. METHODS: 119 patients with IRAAA were electively operated by the same surgeon between January 1, 2006 and December 31, 2015, following selection for OSR or EVAR according to surgical risk. Complications, reinterventions, failures, and early and late mortality were analyzed. RESULTS: 63 OSR and 56 EVAR patients were analyzed. They were similar in terms of age (70 years), gender (92% men), and average diameter of IRAAA (6.5 cm), but with different comorbidities, surgical risk, and anatomy. EVAR was better than OSR regarding time in the operating theatre (177.5 vs. 233.3 minutes), need for transfusion (25 vs. 73%), and length of stay in ICU (1.3 vs. 3.3 days) and hospital (8.1 vs. 11.1 days). OSR allowed more associated procedures to be conducted simultaneously (19.0 vs. 1.8%). There were no significant differences between the groups with respect to complications (25.4 vs. 25.1%), reinterventions (3.2 vs. 5.2%), or early mortality (1.6 vs. 0%). During follow-up, OSR was associated with fewer revisions (3.13 vs. 4.21), angio-CTs (0.22 vs. 3.23), complications (6.4 vs. 37.5%), reinterventions (3.2 vs. 23.2%), and failures (1.6 vs. 10.7%), and had better survival (78.2 vs. 63.2%). CONCLUSIONS: Correct selection of patients achieves excellent results because it avoids OSR in patients at high risk and avoids EVAR in patients with high anatomical complexity, achieving similar results in the perioperative period, but better results for OSR over the course of follow-up.

CONTEXTO: A cirurgia aberta (CA) e o reparo endovascular de aneurisma (REVA) são tratamentos alternativos para o aneurisma da aorta abdominal infrarrenal (AAAIR). OBJETIVOS: Comparar CA e REVA no tratamento do AAAIR. MÉTODOS: Foram incluídos 119 pacientes com AAAIR, operados eletivamente pelo mesmo cirurgião entre 1 de janeiro de 2006 e 31 de dezembro de 2015, após seleção para CA ou REVA de acordo com o risco cirúrgico. Complicações, reintervenções, falhas e mortalidade precoce e tardia foram analisadas. RESULTADOS: Foram analisados 63 pacientes de CA e 56 de REVA, com semelhanças de idade (70 anos), sexo (92% homens) e diâmetro médio do AAAIR (6,5 cm), mas com diferentes comorbidades, riscos cirúrgicos e anatomias. O REVA foi melhor que a CA em relação ao tempo na sala de cirurgia (177,5 vs. 233,3 minutos), necessidade de transfusão (25 vs. 73%) e tempo de permanência na unidade de terapia intensiva (1,3 vs. 3,3 dias) e no hospital (8,1 vs. 11,1 dias). A CA permitiu que mais procedimentos associados fossem realizados simultaneamente (19,0 vs. 1,8%). Não houve diferenças significativas entre os grupos em relação a complicações (25,4 vs. 25,1%), reintervenções (3,2 vs. 5,2%) e mortalidade precoce (1,6 vs. 0%). Durante o acompanhamento, a CA apresentou menos revisões (3,13 vs. 4,21), angiotomografias (0,22 vs. 3,23), complicações (6,4 vs. 37,5%), reintervenções (3,2 vs. 23,2%) e falhas (1,6 vs. 10,7%), além de ter melhor sobrevida (78,2 vs. 63,2%). CONCLUSÕES: A seleção correta dos pacientes proporciona excelentes resultados porque evita pacientes com alto risco para CA e com complexidade anatômica para REVA. Os resultados são semelhantes no período perioperatório, mas melhores para CA durante o acompanhamento.

Early and late results of open surgical and endovascular treatment of infrarenal abdominal aortic aneurysms, selected according to surgical risk / Resultados precoces e tardios dos tratamentos aberto e endovascular de aneurismas da aorta abdominal infrarrenal, selecionados de acordo com o risco cirúrgico

Abstract Background Open surgical repair (OSR) and endovascular aneurysm repair (EVAR) surgery are alternative treatments for infrarenal abdominal aortic aneurysm (IRAAA). Objectives To compare OSR and EVAR for the treatment of IRAAA. Methods 119 patients with IRAAA were electively operated by the same surgeon between January 1, 2006 and December 31, 2015, following selection for OSR or EVAR according to surgical risk. Complications, reinterventions, failures, and early and late mortality were analyzed. Results 63 OSR and 56 EVAR patients were analyzed. They were similar in terms of age (70 years), gender (92% men), and average diameter of IRAAA (6.5 cm), but with different comorbidities, surgical risk, and anatomy. EVAR was better than OSR regarding time in the operating theatre (177.5 vs. 233.3 minutes), need for transfusion (25 vs. 73%), and length of stay in ICU (1.3 vs. 3.3 days) and hospital (8.1 vs. 11.1 days). OSR allowed more associated procedures to be conducted simultaneously (19.0 vs. 1.8%). There were no significant differences between the groups with respect to complications (25.4 vs. 25.1%), reinterventions (3.2 vs. 5.2%), or early mortality (1.6 vs. 0%). During follow-up, OSR was associated with fewer revisions (3.13 vs. 4.21), angio-CTs (0.22 vs. 3.23), complications (6.4 vs. 37.5%), reinterventions (3.2 vs. 23.2%), and failures (1.6 vs. 10.7%), and had better survival (78.2 vs. 63.2%). Conclusions Correct selection of patients achieves excellent results because it avoids OSR in patients at high risk and avoids EVAR in patients with high anatomical complexity, achieving similar results in the perioperative period, but better results for OSR over the course of follow-up.

Resumo Contexto A cirurgia aberta (CA) e o reparo endovascular de aneurisma (REVA) são tratamentos alternativos para o aneurisma da aorta abdominal infrarrenal (AAAIR). Objetivos Comparar CA e REVA no tratamento do AAAIR. Métodos Foram incluídos 119 pacientes com AAAIR, operados eletivamente pelo mesmo cirurgião entre 1 de janeiro de 2006 e 31 de dezembro de 2015, após seleção para CA ou REVA de acordo com o risco cirúrgico. Complicações, reintervenções, falhas e mortalidade precoce e tardia foram analisadas. Resultados Foram analisados 63 pacientes de CA e 56 de REVA, com semelhanças de idade (70 anos), sexo (92% homens) e diâmetro médio do AAAIR (6,5 cm), mas com diferentes comorbidades, riscos cirúrgicos e anatomias. O REVA foi melhor que a CA em relação ao tempo na sala de cirurgia (177,5 vs. 233,3 minutos), necessidade de transfusão (25 vs. 73%) e tempo de permanência na unidade de terapia intensiva (1,3 vs. 3,3 dias) e no hospital (8,1 vs. 11,1 dias). A CA permitiu que mais procedimentos associados fossem realizados simultaneamente (19,0 vs. 1,8%). Não houve diferenças significativas entre os grupos em relação a complicações (25,4 vs. 25,1%), reintervenções (3,2 vs. 5,2%) e mortalidade precoce (1,6 vs. 0%). Durante o acompanhamento, a CA apresentou menos revisões (3,13 vs. 4,21), angiotomografias (0,22 vs. 3,23), complicações (6,4 vs. 37,5%), reintervenções (3,2 vs. 23,2%) e falhas (1,6 vs. 10,7%), além de ter melhor sobrevida (78,2 vs. 63,2%). Conclusões A seleção correta dos pacientes proporciona excelentes resultados porque evita pacientes com alto risco para CA e com complexidade anatômica para REVA. Os resultados são semelhantes no período perioperatório, mas melhores para CA durante o acompanhamento.

Modelo predictivo de metástasis en ganglios axilares no centinela en cáncer de mama. Variables emergentes. Estudio MOTTO, parte I / Predictive model of breast cancer metastasis in axillary non-sentinel lymph nodes. Emergent variables. The MOTTO study, part I

INTRODUCCIÓN: La carga tumoral total (CTT) obtenida del estudio OSNA de cada uno de los ganglios centinela ha sido identificada como el predictor más potente de metástasis en ganglios linfáticos axilares no centinela. Por otra parte, los distintos subtipos moleculares (SM) de cáncer de mama difieren entre ellos de forma significativa no solo en términos de incidencia, pronóstico y tratamiento, sino también respecto al patrón de afectación metastásica axilar. Nuestra hipótesis consiste en que la predicción de enfermedad metastásica en la linfadenectomía axilar puede mejorar aplicando un modelo predictivo basado en la CTT y el subtipo intrínseco del tumor. OBJETIVO: Evaluar el impacto del SM subrogado inmunohistoquímicamente en la predicción metastásica de los ganglios axilares no centinela con base en la CTT. MATERIAL Y MÉTODOS: Estudio retrospectivo, multicéntrico europeo, que incluye 683 pacientes procedentes de 9 hospitales. RESULTADOS: El análisis univariante identificó 6 variables independientes que correlacionan significativamente con la afectación metastásica axilar no centinela. De ellas, las variables valor logarítmico de la CTT, diámetro tumoral y SM diagnosticado por inmunohistoquímica fueron seleccionadas para el modelo multivariante. Las odds ratio estimadas por el modelo fueron valor logarítmico de la CTT 1.527 (IC 95% 1.299-1.796), diámetro tumoral 1.503 (IC 95% 1.062-2.129) y SM 2.195 (IC 95% 1.246-3.867). CONCLUSIONES: El SM, la CTT y el diámetro tumoral son los predictores más potentes de afectación axilar y deben ser incluidos en los algoritmos diagnósticos como variables esenciales para la toma de decisiones terapéuticas sobre la axila

INTRODUCTION: The total tumour load (TTL) obtained from OSNA study in each of the sentinel lymph nodes has been identified as the most powerful predictor of axillary non-sentinel lymph node metastasis. In addition, the distinct molecular subtypes (MS) of breast cancer differ significantly not only in terms of incidence, prognosis and treatment but also in terms of the pattern of axillary metastatic involvement. We hypothesised that the prediction of metastatic disease in axillary lymphadenectomy could be enhanced by applying a predictive model based on the TTL and the intrinsic tumour subtype. OBJECTIVE: To evaluate the impact of the MS identified by immunohistochemistry on prediction of metastatic disease in axillary non-sentinel lymph nodes based on TTL. MATERIAL AND METHODS: Retrospective, European multicenter study including 683 patients from 9 hospitals. RESULTS: Univariate analysis identified 6 variables that were significantly correlated with axillary non-sentinel metastasis. Of these, the variables logarithmic value of the TTL, tumour diameter and MS diagnosed by immunohistochemistry were selected for multivariate analysis. The odds ratio estimated by the model were: logarithmic value of the TTL 1.527 (95% CI: 1.299-1.796), tumour diameter 1.503 (95% CI: 1.062-2.129) and MS 2.195 (95% CI: 1.246-3.867). CONCLUSIONS: The strongest predictors of axillary involvement were MS, TTL and tumour diameter. These variables should be included in diagnostic algorithms as essential parameters for therapeutic decision-making on the axilla

Control de calidad de la citología ginecológica. Programa de Calidad de la Sociedad Española de Citología. Resultados de la primera ronda / Quality control of Gynecologic cytology program of the Spanish sicuety for Cytology. Results of the first round

Introducción. Las recomendaciones del cribado de cáncer de cérvix en España incluyen la participación en programas de control de calidad externos a los laboratorios de citología. La Sociedad Española de Citología ha iniciado un programa de control de calidad de la citología ginecológica. Objetivo. Presentar y discutir los resultados de la primera ronda del control de calidad de la Sociedad Española de Citología. Material y método. Organización de los hospitales participantes según el tipo de citología. Intercambio de preparaciones de 50 casos entre los participantes: 10 negativos, 20 ASCUS-ASCH, 10 LSIL y 10 HSIL. Estudio de la correlación diagnóstica interobservador. Resultados. Trece hospitales participantes: 6 en ThinPrep, 5 en triple toma y 2 en SurePath. La concordancia global media fue del 69,7%. La concordancia media por tipo de lesión fue del 41,7%. La concordancia en negativos fue del 78,1%, en ASCUS del 41,3%, en LSIL de 58,9% y en HSIL del 64,2%. Los casos discordantes se diagnosticaban con mayor frecuencia como negativos, ASCUS y LSIL. Las discordancias severas (HSIL/ASCH versus negativo), alcanzaron un 3,8% de casos. Conclusiones. Nuestros resultados son similares a los descritos en la literatura con muy escasas discordancias severas. El método de intercambio de laminillas utilizado no permite una formación continuada posterior, ya que no incluye la revisión de los casos con discordancias diagnósticas. Por ello, se contemplan correcciones metodológicas en sucesivas rondas (AU)

Introduction. The Spanish guidelines for cervical cancer screening recommend participating in external quality control programs. The Spanish Society of Cytology has started its own program of quality control for gynecological cytology. Aim. To describe and discuss the results of the first round of The Spanish Society of Cytology quality control for gynecological cytology. Material and method. Organization of participating hospitals on the basis of cytology type. Exchange of diagnostic slides from 50 cases among participants, as follows: 10 negative; 20 ASCUS-ASCH, 10 LSIL and 10 HSIL. Analysis of inter-observer correlation. Results. 13 hospitals took part: 6 with ThinPrep liquid-based cytology, 5 with conventional cytology, and 2 with SurePath liquid-based cytology. The global mean concordance was 69.7%. The mean concordance in the type of lesion was 41.7%. The concordance was 78.1% in negative diagnoses, 41.3%, in ASCUS, 58.9% in LSIL and 64.2% in HSIL The discordant cases were diagnosed more frequently as negative, ASCUS and LSIL. 3.8% of cases showed major discordances (HSIL or ASCH versus negatives). onclusions. Our results are similar to those reported in the literature, with very little severe discordance. The method of exchanging slides does not allows continuous training, since the review of discordant cases can not be made. Therefore, methodological corrections are contemplated for future rounds (AU)

Role of total tumour load of sentinel lymph node on survival in early breast cancer patients.

BACKGROUND: Axillary staging (pN) is considered one of the most important prognostic factors in breast cancer patients. However, the Z0011 study data drastically reduced the number of surgical axillary dissections in a selected group of patients, limiting the prognostic information relating to axillary involvement to the sentinel lymph node (SLN). It is known that there is a relationship between SLN total tumour load (TTL) and axillary involvement. The objective of this study is to analyse the relationship between the TTL and outcomes in patients with early stage breast cancer. PATIENTS AND METHODS: clinicopathological and follow-up data were collected from 950 patients with breast cancer between 2009 and 2010 on whom SLN analysis was conducted by molecular methods (One Step Nucleic Acid Amplification, Sysmex, Kobe, Japan). RESULTS: TTL (defined as the total number of CK19 mRNA copies in all positive SLN) correlates with disease free survival (HR, 1.08; p = 0.000004), with local recurrence disease free survival (HR = 1.07; p = 0.0014) and overall survival (HR: 1.08, p = 0.0032), clearly defining a low-risk group (TTL <2.5 × 104 CK19 mRNA copies/µL) versus a high-risk group (>2.5 × 104 CK 19 mRNA copies/µL). CONCLUSIONS: SLN TTL permits the differentiation between two patient groups in terms of DFS and OS, independently of axillary staging (pN), age and tumour characteristics (size, grade, lymphovascular invasion). This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed.

Müllerianosis with Intestinal Metaplasia: A Case Report.

Müllerianosis or Müllerian choristomas are developmental alterations that consist of an organoid structure with normal Müllerian tissue. We present a 62-year-old patient diagnosed on ultrasound scanning and on CT scan of bilateral ovarian cysts. During surgery, a left ovarian cyst and retroperitoneal tumor (adhered to sigmoid serous surface) were found. On histological examination, the tumor corresponded with a Müllerian choristoma showing endometrial, endosalpingeal and endocervical epithelium, with foci of intestinal metaplasia, a phenomenon not described in the literature.

Ultrasound-guided excision combined with intraoperative assessment of gross macroscopic margins decreases the rate of reoperations for non-palpable invasive breast cancer.

AIMS: The standard technique for intraoperative tumour localization of clinically occult tumours is wire-guided localization (WGL). This, however, this has several disadvantages. The aim of the present work is to report our single-centre experience with intraoperative ultrasound-guided (IOUS) excision, performed by surgeons, combined with intraoperative assessment of macroscopic pathologic and ultrasound margins in non-palpable invasive cancers indicated for conservative breast therapy. PATIENTS AND METHODS: Two-hundred and twenty-five non-palpable invasive breast cancers were subjected to excision with IOUS. The lesion was located in the operating room with a high-frequency ultrasound probe (8-12 MHz), which was then used to guide surgical removal. The specimen margins were estimated by ultrasonography and macroscopic pathologic examination. The sensitivity of IOUS and effectiveness in the characterization of the specimen margins were evaluated, assessing the need for reoperation. RESULTS: Pathologic tumour size was 12.0 ± 6.7 mm and 13 lesions (6.4 %) were <5 mm. The sensitivity of IOUS localization was 99.6% (224/225 cases). Only one cancer of less than 5 mm was not localized. The average weight of the specimens was 26.1 g. A second operation was required to remove margins in the 4% of cases (9/225). In 5 cases remains of in situ or invasive carcinoma were found. In two cases, conservative surgery was converted to mastectomy. CONCLUSIONS: IOUS excision combined with the intraoperative assessment of the macroscopic margins of non-palpable breast cancers is a safe, useful, and efficient technique. We obtained an excellent characterization of tumour margins with moderate removal of breast tissue and consequently a lower number of reoperations were required and good cosmetic results were obtained. We believe that use of this technique in conservative breast cancer surgery should be recommended.

Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas.

BACKGROUND: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. METHODS: Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; RESULTS: Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders). Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups of samples: those discriminated by tumour location and, the most importantly, the group discriminated by their proliferative potential; CONCLUSIONS: Primary glioblastomas could be sub-classified according to the properties of their CD133+ cells. The molecular characterization of these potential stem cell populations could be critical to find new therapeutic targets and to develop an effective therapy for these tumours with very dismal prognosis.