Peritumoral immune infiltrates in primary tumours are not associated with the presence of axillary lymph node metastasis in breast cancer: a retrospective cohort study.

BACKGROUND: The axillary lymph nodes (ALNs) in breast cancer patients are the body regions to where tumoral cells most often first disseminate. The tumour immune response is important for breast cancer patient outcome, and some studies have evaluated its involvement in ALN metastasis development. Most studies have focused on the intratumoral immune response, but very few have evaluated the peritumoral immune response. The aim of the present article is to evaluate the immune infiltrates of the peritumoral area and their association with the presence of ALN metastases. METHODS: The concentration of 11 immune markers in the peritumoral areas was studied in 149 patients diagnosed with invasive breast carcinoma of no special type (half of whom had ALN metastasis at diagnosis) using tissue microarrays, immunohistochemistry and digital image analysis procedures. The differences in the concentration of the immune response of peritumoral areas between patients diagnosed with and without metastasis in their ALNs were evaluated. A multivariate logistic regression model was developed to identify the clinical-pathological variables and the peritumoral immune markers independently associated with having or not having ALN metastases at diagnosis. RESULTS: No statistically significant differences were found in the concentrations of the 11 immune markers between patients diagnosed with or without ALN metastases. Patients with metastases in their ALNs had a higher histological grade, more lymphovascular and perineural invasion and larger-diameter tumours. The multivariate analysis, after validation by bootstrap simulation, revealed that only tumour diameter (OR = 1.04; 95% CI [1.00-1.07]; p = 0.026), lymphovascular invasion (OR = 25.42; 95% CI [9.57-67.55]; p < 0.001) and histological grades 2 (OR = 3.84; 95% CI [1.11-13.28]; p = 0.033) and 3 (OR = 5.18; 95% CI [1.40-19.17]; p = 0.014) were associated with the presence of ALN metastases at diagnosis. This study is one of the first to study the association of the peritumoral immune response with ALN metastasis. We did not find any association of peritumoral immune infiltrates with the presence of ALN metastasis. Nevertheless, this does not rule out the possibility that other peritumoral immune populations are associated with ALN metastasis. This matter needs to be examined in greater depth, broadening the types of peritumoral immune cells studied, and including new peritumoral areas, such as the germinal centres of the peritumoral tertiary lymphoid structures found in extensively infiltrated neoplastic lesions.

Solid carcinoma is a variant of microcystic adnexal carcinoma: A 14-case series.

BACKGROUND: Solid carcinoma is a poorly characterized malignant apocrine neoplasm as only 16 cases have been published. OBJECTIVE: To characterize its clinical, histopathological, and immunohistochemical features. METHODS: We compiled 14 cases of solid carcinoma and clinical information were updated. Hematoxylin and eosin slides were reviewed and we stained all the cases for CEA, EMA, SMA, PHLDA-1, BerP4, nestin, p53, p63, p75, CK5/6, CK7 and some with remaining material for CK14, 15, CK10, CK19, S100, CD117, and CAM5. RESULTS: All the lesions were located on the scalp. Histopathologically, all the cases were characterized by solid aggregates of neoplastic epithelial cells without nuclear atypia or mitotic figures involving all the dermis. All the cases presented perineural infiltration and most of them had cornified cystic structures. CK5/6 and p63 were positive. CEA and EMA underlined the scarce ducts. Ki67 was lower than 1%. BerEP4 and PHLDA-1 were negative. CONCLUSION: Solid carcinoma is a solid variant of MAC affecting the scalp more frequently than classic MAC, mostly in old males and showing variable-sized nests involving the entire dermis and composed by poroid, clear-cells, or a mixture of both. It is positive for p63 and CK5/6 and negative for BerEP4 and PHLDA-1. Staining features with CK19 and PHLDA1 differ from classic MAC.

Estudio comparativo de la supervivencia del cáncer de mama según diagnóstico asistencial versus programa de detección precoz / Comparison of breast cancer survival by diagnosis in the clinical setting versus screening

Objetivo. Comparar la supervivencia del cáncer de mama en mujeres que han sido cribadas en el programa de Detección Precoz del Cáncer de Mama (DPCM) y en las que no han participado en él. Pacientes y métodos. Es un estudio descriptivo y longitudinal en el que se han estudiado todos los cánceres de mama registrados en el servicio de Anatomía Patológica del Hospital de Tortosa Verge de la Cinta (Tarragona) de mujeres de 50-65 años, que se habían detectado la enfermedad ellas mismas o que la había detectado el programa DPCM, desde junio de 1999 hasta junio de 2003. Se registraron 101 pacientes con cáncer de mama, de las que en 84 se pudieron recoger todos los datos relativos al tumor, la cirugía y el tratamiento. En el 2014, tras un seguimiento de 11,6 ± 1,8 años, se anotó el estado actual. Resultados. No hay diferencia estadísticamente significativa en la supervivencia de los 2 grupos. Pacientes con carcinoma in situ y sin ganglios metastásicos se encuentran entre las fallecidas, mientras que ninguna paciente con carcinoma bien diferenciado falleció. Conclusiones. En nuestro estudio, el cribado del cáncer de mama no mejora la supervivencia y determinados factores en los que se apoyan los programas de cribado, como la detección de carcinomas no infiltrantes y/o de ganglios no metastásicos, no aseguran la curación (AU)

Objective. To compare survival in breast cancer between women diagnosed in an early breast cancer detection programme and those not attending this programme. Patients and methods. We conducted a descriptive and longitudinal study that analysed all types of breast cancer registered in the Pathology Service of the Hospital de Tortosa Verge de la Cinta (Tarragona, Spain). Tumour samples were obtained from 50-65-year-old women who had detected alterations on self-examination and from those attending the early breast cancer detection programme from June 1999 to June 2003. All the information relating to the tumour, surgery or treatment was registered. In 2014, after a follow-up of 11.6 ± 1.8 years, the current status of each patient was recorded. Results. There was no significant statistical difference in survival between the two groups of patients. Non-survivors included patients with in situ carcinoma and without lymph node metastases. Survival was 100% in patients with well differentiated carcinoma. Conclusions. Breast cancer screening did not improve survival in our study. The elements on which screening programs are based, such as non-invasive carcinoma detection and/or non- metastatic lymph nodes, do not ensure recovery (AU)

El circuito asistencial de la fibrilación auricular en pacientes ambulatorios: estudio observacional Audit fibrilación auricular en el Baix Ebre / The management of atrial fibrillation and characteristics of its current care in outpatients. AFABE observational study

OBJETIVO: Conocer el circuito asistencial de la fibrilación auricular (FA): diagnóstico, tratamiento y seguimiento en el contexto asistencial del sistema sanitario público. DISEÑO: AFABE es un estudio observacional, multicéntrico y descriptivo, con datos retrospectivos relacionados con el diagnóstico, tratamiento y seguimiento de una cohorte de pacientes ambulatorios con FA en el contexto de la atención primaria, servicios de urgencias y cardiología referentes. Emplazamiento: Atención primaria y especializada. Comarca del Baix Ebre. Tarragona. España. Participantes: Muestra representativa de pacientes con FA > 60 años, seleccionados aleatoriamente entre los pacientes registrados en los 22 centros de atención primaria existentes en el territorio del estudio. Mediciones principales: Datos demográficos, comorbilidades, valor CHA2DS2-VASc y HAS_BLED, y patrones asistenciales resultantes entre la atención primaria y servicios referentes. RESULTADOS: Se incluyeron 182 pacientes, de 78,5; DE:7,3 años, y el 50% mujeres. En atención primaria (AP) se realizó el primer contacto en el 68,3% (IC 95% 60,3-76,3) de los casos de FA, de los que un 56,3% (IC 95% 45,2-66,0) fueron enviados al servicio de urgencias del hospital referente. El 72,7% (IC 95% 63,5-79,0) de los tratamientos anticoagulantes orales y el 58,44% (IC 95% 49,4-66,9) de los tratamientos antiarrítmicos se iniciaron en el servicio de urgencias referente. Un 55,9% (IC 95% 47,2-64,7) de los pacientes son seguidos por el servicio de cardiología referente. CONCLUSIONES: El médico de AP realiza el primer contacto de la mayoría de FA y deriva el 55% de los casos al servicio de urgencias hospitalario donde se inician la mayoría de tratamientos específicos de la FA

AIM: To provide insights into the characteristics and management of outpatients when their atrial fibrillation (AF) was first detected: diagnosis, treatment and follow-up in the context of the public health system. DESIGN: AFABE is an observational, multicentre descriptive study with retrospective data collection relating to the practice patterns, management and initial strategies of treatment of patients with diagnosed AF in the context of primary care, emergency and cardiologists of the public health system. Setting: Primary and Specialist care. Baix Ebre region. Tarragona. Spain. Subjects: A representative sample of 182 subjects > 60-year-old with AF who have been randomized, recruited among the registered patients with AF in 22 primary care centres in the area of the study. Mesurements: Demographic data, comorbidities (AF), CHA2DS2-VASc and HAS BLED scores, and practice patterns results between Primary Care and referral services. RESULTS: A total of 182 patients were included (mean age 78.5 SD: 7.3 years; 50% women). Most patients (68.3% 95%CI; 60.3-76.3) had the first contact in Primary Care, of which 56.3% (95%CI;45.2-66.0) were sent to Hospital Emergency Department where 72.7% (95%CI: 63.5-79.0) of the oral anticoagulation and 58.4% (95%CI: 49.4-66.9) of antiarrhytmic treatments were started. More than half (55.9%:95%CI; 47.2-64.7, of patients with permanent AF were followed-up by the Cardiology department. CONCLUSIONS: Most patients with newly diagnosed AF made a first contact with Primary Care, but around half were sent to Hospital Emergency departments, where they were treated with an antiarrhythmic and/or oral anticoagulation

[The management of atrial fibrillation and characteristics of its current care in outpatients. AFABE observational study]. / El circuito asistencial de la fibrilación auricular en pacientes ambulatorios: estudio observacional Audit fibrilación auricular en el Baix Ebre.

AIM: To provide insights into the characteristics and management of outpatients when their atrial fibrillation (AF) was first detected: diagnosis, treatment and follow-up in the context of the public health system. DESIGN: AFABE is an observational, multicentre descriptive study with retrospective data collection relating to the practice patterns, management and initial strategies of treatment of patients with diagnosed AF in the context of primary care, emergency and cardiologists of the public health system. SETTING: Primary and Specialist care. Baix Ebre region. Tarragona. Spain. SUBJECTS: A representative sample of 182 subjects > 60-year-old with AF who have been randomized, recruited among the registered patients with AF in 22 primary care centres in the area of the study. MESUREMENTS: Demographic data, comorbidities (AF), CHA2DS2-VASc and HAS_BLED scores, and practice patterns results between Primary Care and referral services. RESULTS: A total of 182 patients were included (mean age 78.5 SD:7.3 years; 50% women). Most patients (68.3% 95%CI; 60.3-76.3) had the first contact in Primary Care, of which 56.3% (95%CI; 45.2-66.0) were sent to Hospital Emergency Department where 72.7% (95%CI: 63.5-79.0) of the oral anticoagulation and 58.4% (95%CI: 49.4-66.9) of antiarrhytmic treatments were started. More than half (55.9%:95%CI; 47.2-64.7, of patients with permanent AF were followed-up by the Cardiology department. CONCLUSIONS: Most patients with newly diagnosed AF made a first contact with Primary Care, but around half were sent to Hospital Emergency departments, where they were treated with an antiarrhythmic and/or oral anticoagulation.

Atrial Fibrillation and Cardiovascular Comorbidities, Survival and Mortality: A Real-Life Observational Study.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia encountered in clinical practice affecting up to 10% of the population over 60 years old and its prevalence rises with age. The main goals were to characterize the AF patient population after the initial diagnosis of AF and to determine overall survival. METHODS: It is a real-life observational study of 269 subjects with an AF diagnosis over 60 years old randomly selected. The collected variables were: sociodemographic, cardiovascular complications/comorbidities (CVCs) included in the CHA2DS2-VASc and HAS_BLED scores, drug assigned as clinical treatment, mean range INR and CVCs and death dates (all-cause mortality). The survival curve and the risk of death were assessed using Kaplan-Meier survival curve and comparisons with log-rank. RESULTS: The average following time was 6.2 ± 3.7 years (0.2-20.4). Eleven point five percent died. Sixty-five point four percent had some CVCs. There were no differences in the overall incidence of CVCs by gender. The survival probability was 0.86 ± DE 0.03 among men and 0.90 ± DE 0.04 among women without differences. Thirty-six point eight percent (95% CI: 30.8 - 42.7) were diagnosed vascular complications before AF diagnosis, being ischemic cardiopathy (24.2%) and ischemic stroke (23.2%) the most frequent. The mortality is higher (P < 0.036) among those who suffered ≥ 3 vascular complications and significantly lower among those treated with statins (P = 0.032). After AF diagnosis, the most frequent was the cardiac heart failure (46.7%), significantly higher among women (P = 0.037). The mortality is significantly lower in those treated with OAC (P = 0.003). CONCLUSIONS: AF is associated with ischemic heart disease, ischemic stroke and congestive heart failure, but the average mortality age is not different from the global population in Spain and Catalonia.

Prevalencia de la fibrilación auricular desconocida y la no tratada con anticoagulantes. Estudio AFABE / Prevalence of undiagnosed atrial fibrillation and of that not being treated with anticoagulant drugs: the AFABE study

Introducción y objetivos. La fibrilación auricular significa un grave problema de salud pública por sus complicaciones, por lo que su manejo debería incluir no sólo su tratamiento, sino también la prevención de las complicaciones tromboembólicas. El objetivo principal es conocer las proporciones de la fibrilación auricular desconocida y la no tratada con anticoagulantes. Métodos. Estudio observacional, transversal, retrospectivo, de base poblacional y multicéntrico. Se seleccionó aleatoriamente a 1.043 sujetos mayores de 60 años para realizarles un electrocardiograma en visita concertada. Se registraron variables sociodemográficas, valores en las escalas CHA2DS2-VASc y HAS-BLED, razón internacional normalizada y motivos de no recibir tratamiento anticoagulante oral. Resultados. La prevalencia total de fibrilación auricular fue del 10,9% (intervalo de confianza del 95%, 9,1-12,8%), de la que el 20,1% era desconocida. De la fibrilación auricular conocida, el 23,5% con un valor de CHA2DS2-VASc ≥ 2 no recibía tratamiento anticoagulante y el 47,9% tenía un valor HAS-BLED ≥ 3. La odds ratio de no recibir tratamiento anticoagulante fue 2,04 (intervalo de confianza del 95%, 1,11-3,77) para las mujeres, 1,10 (intervalo de confianza del 95%, 1,05-1,15) para la mayor edad de diagnóstico y 8,61 (intervalo de confianza del 95%, 2,38-31,0) si el valor de CHA2DS2-VASc es < 2. El deterioro cognitivo (15,2%) fue el motivo principal de no recibir tratamiento anticoagulante. Conclusiones. El 20,1% de las fibrilaciones auriculares de pacientes mayores de 60 años son desconocidas previamente y no se trata con anticoagulantes al 23,5% del total (AU)

Introduction and objectives. Atrial fibrillation constitutes a serious public health problem because it can lead to complications. Thus, the management of this arrhythmia must include not only its treatment, but antithrombotic therapy as well. The main goal is to determine the proportion of cases of undiagnosed atrial fibrillation and the proportion of patients not being treated with oral anticoagulants. Methods. A multicenter, population-based, retrospective, cross-sectional, observational study. In all, 1043 participants over 60 years of age were randomly selected to undergo an electrocardiogram in a prearranged appointment. Demographic data, CHA2DS2-VASc and HAS-BLED scores, international normalized ratio results, and reasons for not receiving oral anticoagulant therapy were recorded. Results. The overall prevalence of atrial fibrillation was 10.9% (95% confidence interval, 9.1%-12.8%), 20.1% of which had not been diagnosed previously. In the group with known atrial fibrillation, 23.5% of those with CHA2DS2-VASc≥2 were not receiving oral anticoagulant therapy, and 47.9% had a HAS-BLED score≥3. The odds ratio for not being treated with oral anticoagulation was 2.04 (95% confidence interval, 1.11-3.77) for women, 1.10 (95% confidence interval, 1.05-1.15) for more advanced age at diagnosis, and 8.61 (95% confidence interval 2.38-31.0) for a CHA2DS2-VASc score<2. Cognitive impairment (15.2%) was the main reason for not receiving oral anticoagulant therapy. Conclusions. The prevalence of previously undiagnosed atrial fibrillation in individuals over 60 years of age is 20.1%, and 23.5% of those who have been diagnosed receive no treatment with oral anticoagulants (AU)

Prevalence of undiagnosed atrial fibrillation and of that not being treated with anticoagulant drugs: the AFABE study.

INTRODUCTION AND OBJECTIVES: Atrial fibrillation constitutes a serious public health problem because it can lead to complications. Thus, the management of this arrhythmia must include not only its treatment, but antithrombotic therapy as well. The main goal is to determine the proportion of cases of undiagnosed atrial fibrillation and the proportion of patients not being treated with oral anticoagulants. METHODS: A multicenter, population-based, retrospective, cross-sectional, observational study. In all, 1043 participants over 60 years of age were randomly selected to undergo an electrocardiogram in a prearranged appointment. Demographic data, CHA2DS2-VASc and HAS-BLED scores, international normalized ratio results, and reasons for not receiving oral anticoagulant therapy were recorded. RESULTS: The overall prevalence of atrial fibrillation was 10.9% (95% confidence interval, 9.1%-12.8%), 20.1% of which had not been diagnosed previously. In the group with known atrial fibrillation, 23.5% of those with CHA2DS2-VASc≥2 were not receiving oral anticoagulant therapy, and 47.9% had a HAS-BLED score≥3. The odds ratio for not being treated with oral anticoagulation was 2.04 (95% confidence interval, 1.11-3.77) for women, 1.10 (95% confidence interval, 1.05-1.15) for more advanced age at diagnosis, and 8.61 (95% confidence interval 2.38-31.0) for a CHA2DS2-VASc score<2. Cognitive impairment (15.2%) was the main reason for not receiving oral anticoagulant therapy. CONCLUSIONS: The prevalence of previously undiagnosed atrial fibrillation in individuals over 60 years of age is 20.1%, and 23.5% of those who have been diagnosed receive no treatment with oral anticoagulants.

Tumor-infiltrating cells as a prognostic factor in Hodgkin's lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients.

The present study aimed to describe the general tissular composition of the immune infiltrate observed in Hodgkin's lymphoma (HL) and its possible relationship with clinical and survival prognostic factors. In this retrospective study of 267 HL patients, the relative proportions of infiltrating T lymphocytes (CD4+, CD8+), natural killer cells (CD 56+, CD 57+), cytotoxic cells (Granzyme B+, TIA-1+) and dendritic cells (CD 21+, S-100+) were quantified immunohistochemically with tissue microarray technology. Our results confirm the predominance of CD4 + T lymphocytes in the background of tumoral cells, in addition to a high number of cytotoxic lymphocytes (CD8, CD 57 and TIA-1). Patients with low numbers of infiltrating CD8, CD 56, CD 57+cells and high numbers of Granzyme B and TIA-1+cells presented a significantly unfavourable clinical course (presence of leukocytosis, B symptoms, advanced clinical stage (III/IV), non-responding patients). A reduced infiltration of CD4+T lymphocytes was related with the presence of Epstein - Barr virus. Significantly longer survival times were observed in patients with a high level of infiltrating CD 57, as well as a low level of Granzyme B and TIA-1+cells (log-rank test). When evaluated in a multivariate model, high levels of infiltrating TIA-1 and Granzyme B+cells were shown to be independent prognostic factors that negatively influenced overall survival. The presence of TIA-1+cells was found to be the only unfavorable prognostic factor of event-free survival and disease-free survival. The overall detection of tumor-infiltrating cells in HL confirms the importance of cytotoxic T lymphocyte infiltration (Granzyme B and TIA-1+cells) in these patients. Independently of the classical clinical and pathological features, these cells appear to be an unfavourable prognostic factor in HL and, more particularly, the presence of cytotoxic TIA-1+cells.

Decreased number of granzyme B+ activated CD8+ cytotoxic T lymphocytes in the inflammatory background of HIV-associated Hodgkin's lymphoma.

This study aimed to assess the differences in the cellular composition of the inflammatory reactive background around tumoral cells of classical Hodgkin's lymphomas (cHL) inside and outside the HIV settings. This retrospective study evaluates the infiltrating T lymphocytes (CD4 and CD8), natural killer cells (CD57+ cells), and more especially cytotoxic cells [granzyme B (GrB) and TIA-1+ cells] in the background of 99 EBV+ cHL. Sections from paraffin-embedded tumor samples from nine HIV-infected cHL patients were immunostained, using standard immunohistochemical protocols and were compared to a control group of 90 HIV-noninfected cHL patients. Our clinical and histological data indicate that HIV-infected cHL patients present a higher frequency of mixed cellularity (MC) histological subtypes, more advanced disease stages, a poor response to treatment, and a poor overall survival compared to control patients. In controls, CD4/CD8 and GrB/TIA-1 ratios were determined as 2:1 and 1:2, respectively. The inflammatory infiltrate of HIV-infected patients had a significant reduction of CD4+ T lymphocytes (CD4/CD8 ratio 1:23), a decrease in infiltrating GrB+ cells (activated cytotoxic cells) and an increase in infiltrating TIA+ T cells (mainly nonactivated cytotoxic cells) in these patients (GrB/TIA-1 ratio 1:12). In conclusion, this study highlights an important intratumoral loss of CD4+ T cells (striking inversion in the CD4/CD8 ratio) and a decrease in intratumoral activated cytotoxic T lymphocytes in HIV-associated cHL patients. Further studies are required to confirm these results and to determine the role of these findings on the antitumoral immune response observed in HIV-associated cHL.

Enfermedad de Hodgkin. Papel etiopatogénico del virus de Epstein-Barr en las comarcas de Tarragona / Hodgkin's disease. Etiopathogenic role of EBV in Tarragona (Spain)

Fundamento: Se pretende determinar la proporción de enfermedad de Hodgkin (EH) que expresa el virus de Epstein-Barr (VEB) en nuestro medio. Pacientes y métodos: Se ha realizado un estudio retrospectivo sobre 49 casos de EH usando la técnica inmunohistoquímica LMP-1 y la técnica de hibridación in situ para EBER-1. Resultados: Un 40,8 por ciento (20/49) de los casos expresaba VEB (EBER-1 y/o LMP-1 positivos). Este porcentaje fue significativamente mayor en EH diagnosticadas a pacientes mayores de 55 años y no hubo diferencias por sexo, aunque fue mayor, pero no de forma significativa, en el subtipo histológico de EH de celularidad mixta. Conclusiones: El VEB se asocia a un 40,8 por ciento de las EH en las comarcas de Tarragona (AU)

Actinomicosis. Consideraciones clínicas, diagnósticas y terapéuticas. A propósito de dos casos / Actinomycosis. Clinical, diagnostic and therapeutic considerations. About two cases

Las infecciones por actinomices afectan de forma prioritaria a la región cervicofacial, según las series del 32-55 por ciento del total se desarrollan a ese nivel. Las especies que con más frecuencia las provocan son Actinomyces israelii (78 por ciento) y Arachnia propiónica. Clásicamente se describen formas de actinomicosis de presentación aguda o de desarrollo crónico. Presentamos dos casos de actinomicosis desarrollados en pacientes varones de edad media, provenientes de medio rural. Describimos en primer lugar un caso provocado por el Actinomyces meyeri, en la forma clínica de presentación aguda. Se manifiesta bajo la forma de absceso laterocervical del lado derecho. El segundo caso clínico está localizado en el dorso de lengua y suelo de boca, provocado por el Actinomyces odontolíticus. Su desarrollo acontece lentamente simulando un tumor en ambas localizaciones. Aunque ambos casos corresponden a prototipos clínicos de la actinomicosis los actinomices que las provocan raramente son citados en la literatura médica al respecto (AU)