Rendimiento diagnóstico de la biopsia por punción en tumor filodes de la mama / Diagnostic role of core needle biopsy in phyllodes tumour of the breast

OBJETIVO: Evaluar el rendimiento de la biopsia por punción (BPP) en el diagnóstico de tumor filodes (TF) de la mama. MATERIAL Y MÉTODOS: Se han revisado todos los diagnósticos anatomopatológicos de TF emitidos tanto en BPP como en biopsia quirúrgica (BQ). Se analizan las características clínicas, de imagen y patológicas de los casos y la concordancia diagnóstica entre la BPP y la BQ. RESULTADO: Se han estudiado un total de 87 casos con diagnóstico de TF, 16 en BPP y 71 en BQ. En 18 casos se dispuso de BPP y BQ. Los TFB diagnosticados en BPP fueron: 7 FAD (uno de ellos de la variedad celular), 2 TFB, un TFL, 2TFM y un hamartoma. Dos casos de TFB en BQ habían sido diagnosticados respectivamente en la BPP de fibrosis e hiperplasia. Un TFM en BPP resultó ser un TFL en la BQ. Hubo concordancia diagnóstica en un TFL y un TFM. Se detectaron 5 (27%) falsos negativos y 8 falsos positivos (38%). CONCLUSIONES: El rendimiento de la BPP en el diagnóstico de los TF es bajo con una alta tasa de falsos negativos y falsos positivos. Por ello se aconseja emitir un diagnóstico en la BPP de lesión fibroepitelial con estroma celular dejando pendiente un diagnóstico definitivo a disponer de la BQ

OBJECTIVE: To evaluate the role of core needle biopsy (CNB) in the diagnosis of phyllodes tumour (PT) of the breast. MATERIAL AND METHODS: All pathological diagnoses of PT in both CNB and surgical biopsy (SB) were reviewed. The clinical, imaging and pathological characteristics of the cases and the diagnostic agreement between CNB and SB were analysed. RESULT: A total of 87 cases with a diagnosis of PT, 16 in CNB and 71 in SB, were studied. In 18 cases, CNB and SB were available. Benign PT diagnosed in CNB consisted of: 7 fibroadenomas (one of them cellular), 2 benign PT, 1 borderline PT, 2 malignant PT, and 1 hamartoma. Two cases of benign PT in SB had been diagnosed with CNB as fibrosis and hyperplasia. One PT diagnosed as malignant in CNB was diagnosed as a borderline PT in SB. There was diagnostic agreement in 1 borderline PT and 1 malignant PT. We detected 5 (27%) false negatives and 8 false positives (38%). CONCLUSIONS: The efficiency of CNB in the diagnosis of PT is low, with a high rate of false negatives and false positives. Therefore, it is advisable to suggest a diagnosis of fibroepithelial lesion with cellular stroma in CNB, reserving definitive diagnosis to SB

Indicadores de calidad en el diagnóstico y tratamiento del cáncer para unidades de mama: encuesta nacional / Breast unit quality indicators in the diagnosis and treatment of cancer: A national survey

Objetivo. Establecer el estado actual de las unidades de patología mamaria (UPM) en la utilización de indicadores de calidad del manejo del cáncer de mama. Material y métodos. Se efectuó una búsqueda bibliográfica de indicadores del manejo del cáncer de mama. Con los resultados se confeccionó una encuesta electrónica de 27 preguntas que se envió a 167 UPM censadas en el Grupo de Estudios Senológicos. Se consideraron las respuestas de 33 de las UPM. Resultados. Solo 9 de las UPM que respondieron estaban acreditadas por la SESPM. Los indicadores más utilizados fueron: utilización de informes siguiendo guías estandarizadas en diagnóstico por la imagen, pacientes con cáncer orientadas para tratamiento por un comité multidisciplinar, determinación de factores pronósticos y predictivos en carcinoma infiltrante, y especificación en el informe de la distancia al margen más cercano de la lesión. Por grupos de indicadores los más utilizados fueron los del procedimiento general y anatomía patológica. Las UPM acreditadas utilizan los indicadores con mayor frecuencia que las no acreditadas. Solo 8 de los 20 indicadores eran utilizados por más del 70% de las UPM para el control de calidad de la unidad y no solo del servicio que los origina. Conclusión. El uso de indicadores para el control de calidad es una herramienta ampliamente utilizada en las UPM que han contestado la encuesta, si bien en muchas ocasiones el indicador solo se usa en el servicio que lo origina y no para la evaluación del funcionamiento de la unidad de forma integral (AU)

Objective. To determine the current state of breast pathology units (BPU) in the use of quality indicators in breast cancer management. Material and methods. After a literature research of breast cancer management indicators, a 27-question survey was designed and sent on-line to 167 BPU from the Group for Senology Studies. Completed surveys were considered from 33 BPU. Results. Only 9 of the BPU that responded were accredited by the SESPM. The most commonly used indicators were the following: use of standardised reporting guidelines in imaging diagnosis, patients with breast cancer treated by a multidisciplinary committee, determination of prognostic and predictive factors in invasive carcinoma, and specification of margin distance in the pathologic report. The most widely used indicators were those of the general process and pathology. Use of the indicators was more frequent in accredited than in non-accredited BPU. Only 8 of the 20 indicators were used by more than 70% of BPU for unit quality control and not only by the service creating them. Conclusions. The use of indicators for quality control is a widely used tool in the BPU responding to the survey. However, indicators are often only used in the service creating them and not for integral quality assessment of the BPU (AU)

Preservación de la fertilidad: revisión y análisis de los tiempos oncológicos / Fertility preservation: a review and analysis of cancer treatment times

La incidencia del cáncer de mama (CM) ha aumentado progresivamente y aproximadamente el 15% de las mujeres son diagnosticados antes de los 45 años. Este subgrupo de pacientes suelen tener tumores más agresivos y serán tratadas con terapia sistémica (quimioterapia, terapia hormonal o ambos). Por otra parte, la tendencia a retrasar la edad de maternidad implica que una gran proporción de pacientes con CM jóvenes no han completado su deseo reproductivo. El impacto del tratamiento oncológico en la reserva ovárica depende de la edad de los pacientes, el tipo de esquema y la dosis recibida. El senólogo debería ser sensible al deseo gestacional y realizar una derivación inmediata a la Unidad de Preservación de la Fertilidad. Esta maniobra no implica un retraso en el inicio terapéutico de la enfermedad como demuestran nuestros resultados. En nuestro centro, 40 pacientes fueron sometidas a crioconservación de ovocitos entre 2010 y 2015. La media de días entre el diagnóstico de CM y el inicio del tratamiento oncológico fue de 37,6 días. El tiempo de estimulación (inicio del tratamiento de estimulación hasta la recuperación de los ovocitos) presentó una media de 12 días (7-21). Por lo tanto, consideramos que las pacientes jóvenes deben ser remitidas a una unidad de asesoramiento reproductivo, tal y como aconseja EUSOMA. La preservación de fertilidad requiere de la participación coordinada tanto del equipo de Oncología y el equipo de Reproducción Humana (AU)

The incidence of breast cancer (BC) has progressively increased, and approximately 15% of women will receive a diagnosis before the age of 45 years. This patient subgroup usually has more aggressive tumours and will be treated with systemic therapy (chemotherapy, hormone therapy, or both). In addition, the tendency to delay maternity implies that a many young patients with BC will not have fulfilled their reproductive wishes. The impact of cancer treatment on ovarian reserve depends on patient age, the type of regimen and the doses received. Senologists should be sensitive to their patients’ reproductive wishes and immediately refer them to Fertility Preservation Units. As shown by our results, referral does not imply a delay in treatment initiation. In our centre, 40 patients underwent ovarian tissue cryopreservation between 2010 and 2015. The mean number of days between BC diagnosis and the start of cancer treatment was 37.6 days. The mean time from stimulation (the start of stimulation until oocyte recovery) was 12 days (7-12). Therefore, we believe that young patients should be referred to a reproductive counselling unit, as recommended by EUSOMA. Fertility preservation requires liaison between the oncology and human reproduction teams (AU)

Carcinoma in situ de mama: análisis de los casos y evaluación de las recidivas en nuestro centro, 1999-2012 / Ductal carcinoma in situ: analysis of cases and assessment of recurrences in our center from 1999-2012

Objetivo. Analizar las recidivas de las pacientes diagnosticadas, tratadas y seguidas en nuestro centro por carcinoma ductal in situ de mama, y establecer qué variables se asocian a un mayor riesgo de desarrollarlas. Pacientes y métodos. Se ha realizado un estudio descriptivo retrospectivo de los casos de carcinoma ductal in situ diagnosticados y tratados en nuestro centro desde enero de 1999 hasta enero de 2012. Se excluyeron los casos en que coexistía componente infiltrante y aquellos con antecedente de neoplasia y/o radioterapia previa en la mama afecta. Las variables que se analizaron fueron: la edad de la paciente, el tamaño tumoral, el grado nuclear, el estado de los márgenes quirúrgicos, el tipo de cirugía y el tratamiento complementario (radioterapia y hormonoterapia). Resultados. Se estudiaron 162 casos de carcinomas in situ en el periodo 1999-2012. De estos, 117 (72,2%) fueron tratados con cirugía conservadora y 45 (27,7%) mediante mastectomía. Se produjeron 16 recidivas (9,9%) en el periodo estudiado. No se encuentran diferencias estadísticamente significativas en la tasa de recidivas en función del tamaño tumoral, la distancia quirúrgica al margen, el grado histológico ni la edad de la paciente. En el subgrupo de pacientes tratadas con tumorectomía, la supervivencia libre de enfermedad fue mayor en las que recibieron de forma complementaria radioterapia y hormonoterapia que en aquellas que solo recibieron uno o ninguno de los tratamientos (p=0,001). Conclusión. En el subgrupo de pacientes con carcinoma in situ tratadas con tumorectomía el riesgo de recidiva es 19 veces superior en los casos que no recibieron ningún tratamiento complementario que en aquellos tratados con tumorectomía, radioterapia y hormonoterapia (p=0,001) (AU)

Objective. To analyse recurrences in patients diagnosed, treated and followed up in our centre for ductal carcinoma in situ and to identify the variables associated with an increased risk of their development. Patients and methods. We performed a retrospective study of cases of ductal carcinoma in situ diagnosed and treated in our hospital from January 1999 to January 2012. We excluded cases with coexistence of an infiltrating component, a history of neoplasia, and/or prior radiation to the affected breast. The variables analysed were patient age, tumour size, nuclear grade, surgical margin status, type of surgery, and adjuvant therapy (radiation and hormone therapy). Results. We studied 162 cases of ductal carcinoma in situ occurring between 1999 and 2012. Of these, 117 cases (72.2%) were treated with conservative surgery and 45 (27.7%) by mastectomy. In that period, we found 16 recurrences (9.9%). We found no statistically significant difference in the recurrence rate according to tumour size, surgical distance from the margin, histological grade, or patient age. In the subgroup of patients treated with lumpectomy, disease-free survival was higher in patients receiving radiation therapy and hormone therapy as a complementary treatment than in those who received only one or no treatment at all (P=.001). Conclusion. In the subgroup of patients with ductal carcinoma in situ treated with lumpectomy, the recurrence risk was 19 times higher in patients who received no adjuvant treatment than in those treated with lumpectomy, radiation and hormone therapy (P=.001) (AU)

Breast sarcoma. A case report and review of literature.

INTRODUCTION: Breast sarcomas are rare with an annual incidence of 4.6 cases/1,000,000 women. They can appear as primary forms or secondary to radiation therapy or chronic lymphedema. PRESENTATION OF CASE: A 41 year old woman attended our hospital after having noticed an increase in the size of her fibroadenoma. The examination revealed a 7cm retroareolar nodule. Breast sonography described a hypoechoic bilobulated lesion and MRI showed a large size polinodular image, suggesting a Phyllodes tumor. A core needle biopsy was performed with a histological result of low-grade fusiform cells sarcoma on Phyllodes tumor so we proceeded to surgical treatment with a mastectomy. After two years and a half she noticed a tough nodule over the mastectomy scar, which was resected with a histological result of fusiform cells sarcoma. Considering the diagnosis of recurrence of the disease, surgery was undertaken. DISCUSSION: Breast sarcoma is a rare but aggressive entity. Core biopsy is the procedure of choice for the diagnosis. Lymphatic spread is uncommon so nodal status in breast sarcoma is less informative. Staging study differs from other breast tumors and chest computed tomography is helpful since lungs are the predominant metastatic sites. The use of radiotherapy or chemotherapy is controversial and will depend on the risk of tumor recurrence. CONCLUSION: Surgery represents the only potentially curative therapy for breast sarcoma. Tumor size and adequate resection margin are the most important prognostic factors. Approximately 80% of recurrences appear in the first two years.

Consenso cáncer de mama y fertilidad / Consensus on breast cancer and fertility

El Consenso de Cáncer de Mama y Fertilidad de la Sociedad Española de Senología y Patología Mamaria es un documento elaborado por un amplio grupo de expertos de todas las especialidades implicadas en cáncer de mama. El presente documento se concluyó en el Primer Congreso Español de la Mama, celebrado en Madrid en octubre de 2014, y es una actualización del consenso que fue publicado en Revista de Senología y Patología Mamaria en 2009. Los avances que se están produciendo, tanto en el campo de la fertilidad como en la oncología, obligarán sin ninguna duda a una nueva revisión de las recomendaciones en un futuro cercano (AU)

The Consensus on Breast Cancer and Fertility of the Spanish Society of Senology and Breast Pathology (Sociedad Española de Senología y Patología Mamaria) is a document prepared by a wide group of experts in all the specialties involved in breast cancer. This document was finished at the 1st Spanish Congress on Breast Cancer, held in Madrid in October 2014, and is an update of the consensus document published in Revista de Senología y Patología Mamaria in 2009. Because of the advances currently taking place in the fields of both fertility and oncology, a new review of the recommendations will undoubtedly be needed in the near future (AU)

Utility of specific IgE to Ara h 6 in peanut allergy diagnosis.

BACKGROUND: Specific IgE to Ara h 2 has been shown to be useful in the diagnosis of peanut allergy, whereas the peanut lipid transfer protein, Ara h 9, has been suggested to be responsible for peanut allergy in the Mediterranean population. OBJECTIVE: To better characterize peanut allergy in children from a Mediterranean area and determine the value of specific IgE to Ara h 6 (conglutinin, 2S albumin) for the diagnosis of peanut allergy. METHODS: Ninety-one children with suspected allergy to edible vegetables were included in the study. They were classified as allergic or tolerant to peanut. Specific IgE to peanut allergens was measured by a commercially available microarray (ImmunoCAP ISAC 112, ThermoFisher, Uppsala, Sweden). RESULTS: Patients allergic to peanut showed positive specific IgE changes to peanut seed storage proteins (Ara h 1, Ara h 2, Ara h 3, and Ara h 6) more frequently than tolerant subjects. Ara h 9 showed a similar frequency of reactivity in the 2 groups. Ara h 6 was the allergen most frequently recognized by patients with allergy. Four patients with allergy were found to be mono-sensitized to Ara h 6. Ara h 2 and Ara h 6 showed similar diagnostic accuracy (areas under the curve 0.792 and 0.852). A combined cutoff point for Ara h 2 (≥0.1 ISU) and Ara h 6 (≥2 ISU) yielded the best diagnostic performance (sensitivity 0.77, specificity 0.97, positive predictive value 0.89, negative predictive value 0.93). CONCLUSION: Peanut allergy cannot be ruled out without obtaining a negative determination of Ara h 6.

Shellfish Allergy: a Comprehensive Review.

Shellfish allergy is of increasing concern, as its prevalence has risen in recent years. Many advances have been made in allergen characterization. B cell epitopes in the major allergen tropomyosin have been characterized. In addition to tropomyosin, arginine kinase, sarcoplasmic calcium-binding protein, and myosin light chain have recently been reported in shellfish. All are proteins that play a role in muscular contraction. Additional allergens such as hemocyanin have also been described. The effect of processing methods on these allergens has been studied, revealing thermal stability and resistance to peptic digestion in some cases. Modifications after Maillard reactions have also been addressed, although in some cases with conflicting results. In recent years, new hypoallergenic molecules have been developed, which constitute a new therapeutic approach to allergic disorders. A recombinant hypoallergenic tropomyosin has been developed, which opens a new avenue in the treatment of shellfish allergy. Cross-reactivity with species that are not closely related is common in shellfish-allergic patients, as many of shellfish allergens are widely distributed panallergens in invertebrates. Cross-reactivity with house dust mites is well known, but other species can also be involved in this phenomenon.

Cáncer de mama asociado al embarazo: estudio analítico observacional / Pregnancy-Associated Breast Cancer: An analytical observational study

Fundamento y objetivo: El cáncer de mama asociado al embarazo se define como aquel que aparece durante la gestación o durante el primer año posparto. Pacientes y método: Estudio retrospectivo analítico observacional en el que se comparan 56 cánceres de mama y embarazo (CME) diagnosticados entre 1976-2008 con 73 pacientes con cáncer de mama no asociado al embarazo (CMNE). Se analizan los diversos datos demográficos, los factores pronósticos, el tratamiento y la supervivencia en ambos grupos. Resultados: La prevalencia de CME en nuestro centro es 8,13/10.000 embarazos. La mayor frecuencia (62%) apareció durante el puerperio. Los estadios son mayores en el CME respecto al CMNE, siendo el 31,3% avanzados en el CME frente al 13,3% en el CMNE (p < 0,05). En cuanto a factores pronósticos, el 27,3% de CME eran grado tumoral iii frente al 15,8% del CMNE. En el grupo CME el 33,3% tenían receptores para estrógeno negativos, el 48,7% receptores para progesterona negativos y el 34,5% eran Her2Neu positivo frente al 22,2, 24,1 y 31%, respectivamente, en CMNE. En el 52,8% de CME aparecieron ganglios afectados frente al 33,8% del CMNE (p < 0,05). En el grupo CME la supervivencia global y libre de enfermedad a 5 años fue del 63,7 y del 74,2%, respectivamente. Conclusiones: El peor pronóstico que se observa en el grupo CME es debido posiblemente a la presencia de factores de pronóstico adversos: metástasis ganglionares, receptores hormonales negativos y grado tumoral tipo iii, así como al diagnóstico tardío, con un porcentaje mayor de cánceres avanzados (AU)

Background and objective: Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. Patients and method: A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. Results: The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. Conclusions: The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade III, as well as a delay in diagnosis with a higher rate of advanced stages (AU)

[Pregnancy-Associated Breast Cancer: An analytical observational study]. / Cáncer de mama asociado al embarazo: estudio analítico observacional.

BACKGROUND AND OBJECTIVE: Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. PATIENTS AND METHOD: A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. RESULTS: The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. CONCLUSIONS: The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages.

Peach allergy in Spanish children: tolerance to the pulp and molecular sensitization profile.

BACKGROUND: Peach allergy is the main cause of vegetable food allergy in the Mediterranean area. Pru p 3 is the major allergen, and it is mainly found in the peel. OBJECTIVE: We sought to calculate the frequency of tolerance to peach pulp in Spanish children suffering from allergic reactions after eating or having contact with peach and to analyze the sensitization pattern to peach allergens. METHODS: Fifty-seven children (32 boys; median age, 7.4 yr) were included in the study. A systematized questionnaire on allergic reactions to peach was administered. Prick tests with peach peel and pulp, peach lipid transfer protein (LTP), and profilin were performed. Serum-specific IgE to peach, rPru p 1, rPru p 3, and rPru p 4 was determined by ImmunoCAP. Oral food challenges (OFCs) with peach pulp were performed on all but one child. RESULTS: Eighty-eight percent of the children had positive prick tests with peach peel, 35% with peach pulp, 88% with peach LTP, and 9% with profilin. Serum-specific IgE to peach was demonstrated in 100% of the patients; rPru p 3-specific IgE in 96%; rPru p 1-specific IgE in 11%; and rPru p 4-specific IgE in 10%. Oral food challenge was negative in 52 (93%) children. CONCLUSIONS: More than 90% of the study population tolerated peeled peach. Pru p 3 was the major allergen. Pru p 1 and 4 showed low prevalence.

Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level.

BACKGROUND: Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. OBJECTIVE: To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. METHODS: Thirty-six patients allergic to cow's milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE <3.5 kU/L), 2 (3.5-17 kU/L), and 3 (>17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cow's milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. RESULTS: Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. CONCLUSION: Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels.

Accidental allergic reactions in children allergic to cow's milk proteins.

BACKGROUND: Cow's milk is the main cause of food allergy in children. Patients allergic to food frequently experience accidental exposure. There are few studies analyzing this problem, most of them concerning peanut allergy. OBJECTIVE: We sought to calculate the frequency of accidental exposure reactions in children allergic to cow's milk during a 12-month period, to analyze the clinical characteristics and circumstances surrounding the reactions, and to identify risk factors for severe reactions. METHODS: Eighty-eight children allergic to cow's milk (44 boys; median age, 32.5 months) were included in the study. A systematized questionnaire about accidental exposure was used. Reactions were classified as mild, moderate, and severe. Cow's milk- and casein-specific IgE antibody titers were determined. RESULTS: Thirty-five (40%) children had 53 reactions in the previous year (53% mild, 32% moderate, and 15% severe). Most reactions took place at home (47%) under daily life circumstances (85%). Specific IgE levels to cow's milk were higher in children with severe reactions than in those with moderate (median, 37.70 vs 7.71 KUA/L; P = .04) or mild (3.37 KUA/L; P = .04) reactions. The frequency of severe reactions was 10-fold higher in asthmatic children (odds ratio, 10.2; 95% CI, 1.13-91.54). CONCLUSIONS: Reactions to accidental exposure are frequent in children with cow's milk allergy. The proportion of severe reactions was 15%. The risk factors for such reactions included very high levels of specific IgE to cow's milk and casein and asthma.

Tumor size and lymph node status in multifocal breast cancer.

Tumor size correlates with lymph node metastasis in breast cancer. In multifocal lesions there is controversy about considering the summation of the largest diameter of each tumor. A total of 122 patients with multifocal breast cancer were compared in a retrospective study with 177 patients with unifocal tumors, correlating tumor size with lymph node metastasis. In multifocal tumors, two sizes were considered: the diameter of the largest tumor and the combined diameter of all lesions. Relationship was established by three different logistic models using variables such as age, number of lesions, histologic type, and grade. At a same size of the largest diameter of a unifocal or multifocal lesions and the combined diameter of a multifocal lesion, the latter shows less probability of nodal metastasis indicating that combined diameter is an overestimation of the lesion size. Our results indicate that in multifocal breast cancer, only the diameter of the largest tumor breast cancer has relationship with lymph node metastasis.

Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease.

We aimed to study the expression and localization of the molecular components of enterocyte junctions in celiac disease together with the level of tyrosine phosphorylation, a phenomenon known to affect their cellular distribution and function, and to explore the influence of proinflammatory cytokines. Duodenal biopsy specimens from patients with celiac disease and control subjects were used for immunoprecipitation, immunoblotting, and immunolocalization by using antioccludin, anti-zonula occludens (ZO)-1, anti-E-cadherin, anti-beta-catenin, and antiphosphotyrosine antibodies. The same procedures were carried out on filter-grown Caco-2 cells incubated in the absence or presence of interferon g and tumor necrosis factor a. In active celiac disease, the absence of a phosphorylated ZO-1 and the extensive phosphorylation of beta-catenin might be responsible for the absence of membranous localization of occludin and E-cadherin, respectively. The in vitro system showed an influence of the cytokines on the assembly of these complexes that proved the opposite to celiac samples as far as tight junctions were concerned because the presence of a phosphorylated ZO-1 enables occludin to localize in the membrane.

Influence of retinoic acid on adhesion complexes in human hepatoma cells: a clue to its antiproliferative effects.

Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherinl/beta-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of beta-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.

Prediction of tolerance on the basis of quantification of egg white-specific IgE antibodies in children with egg allergy.

BACKGROUND: It is thought that the natural evolution of food allergy has a good tolerance prognosis. However, there are few follow-up studies that determine the exact probability of tolerance to a given food or that analyze prognostic factors that can help us to understand the evolution of a child who begins life with a food allergy. OBJECTIVE: We sought to determine the likelihood that children younger than 2 years of age with allergy to egg would eventually have tolerance to it and to analyze several prognostic predictors using egg white-specific IgE level as the main variable. METHODS: We performed a prospective study of 58 children younger than 2 years of age with egg allergy, who were studied periodically until tolerance developed or until the end of the study. During the follow-up period, open challenge tests were carried out according to previously established criteria to verify tolerance to egg. Factors such as egg white-specific IgE level, serum total IgE level, symptoms after egg ingestion, size of skin prick test reactions to egg white, atopic dermatitis, and sex were analyzed as prognostic markers. Kaplan-Meier survival curves were used to calculate cumulative tolerance probability. Predictor influence and relative prognostic importance were estimated with the Cox proportional regression model. RESULTS: The median time from the appearance of the first symptoms to tolerance was 35 months. Cumulative tolerance probability was 16% at 12 months of follow-up, 28% at 24 months, 52% at 36 months, 57% at 48 months, and 66% at 60 months. The relative weight of prognostic factors, expressed as the hazard ratio, was 50.95 for symptoms and 3.74 for the size of skin prick test reactions, with both being independent effects. The hazard ratio was 1.173 for every 0.1-unit decrease in the concentration log (decimal logarithm) of specific IgE level, with this effect being associated with tolerance only in children with cutaneous symptoms. CONCLUSIONS: Half of the children younger than 2 years of age with egg allergy will tolerate the food at 35 months of follow-up, and the proportion could be 66% after 5 years. At that age, the main predictors were the symptoms experienced after egg ingestion, followed by the size of skin prick test reactions. In addition, the specific IgE antibody level is an important prognostic marker in children who only had cutaneous symptoms.