Direct introgression of untapped diversity into elite wheat lines.

The effective utilization of natural variation has become essential in addressing the challenges that climate change and population growth pose to global food security. Currently adopted protracted approaches to introgress exotic alleles into elite cultivars need substantial transformation. Here, through a strategic three-way crossing scheme among diverse exotics and the best historical elites (exotic/elite1//elite2), 2,867 pre-breeding lines were developed, genotyped and screened for multiple agronomic traits in four mega-environments. A meta-genome-wide association study, selective sweeps and haplotype-block-based analyses unveiled selection footprints in the genomes of pre-breeding lines as well as exotic-specific associations with agronomic traits. A simulation with a neutrality assumption demonstrated that many pre-breeding lines had significant exotic contributions despite substantial selection bias towards elite genomes. National breeding programmes worldwide have adopted 95 lines for germplasm enhancement, and 7 additional lines are being advanced in varietal release trials. This study presents a great leap forwards in the mobilization of GenBank variation to the breeding pipelines.

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

BACKGROUND: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. METHODS: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. RESULTS: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001). CONCLUSIONS: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.

[Functional outcomes in postsurgery for Hirschsprung´s disease]. / Resultados funcionales en postoperados de enfermedad de Hirschsprung.

OBJECTIVE: To analyze functional outcomes of patients operated for Hirschsprung's disease (HD). METHODS AND MATERIAL: Retrospective study of patients with HD (2000-2014). We analyzed surgical technique, age at diagnostic and treatment, amount of resected bowel, complications and their influence on functional outcomes. RESULTS: Of the 44 diagnosed with HD, 37 were operated in our center. Men 29 (78.4%). With associated pathology 7 (18.9%), and 5 (13.5%) made their debut with enterocolitis. Diagnostic average age 1.04 (0.0 to 7.1 years) and operation average age 1.4 (0.3 to 9.3 years). We did transanal endorectal pull-through (TERPT) in 17 (45.9%) patients and transabdominal approach (TAB) in 20 (54.1%). Received postoperative dilations 8 (21.6%) patients. Functional outcomes were evaluated at an average age of 9.6 (4.7-15.7years) incontinence/soiling were found in 6/28 (21.4%) and constipation in 5/28 (17.9%). The highest rate of incontinence/ soiling was present in 41.7 % TERPT vs. 6.2% TAB (p= 0,036). However, the average age at follow-up in patients with incontinence/soiling was 5.9 ± 1.3 years old, less than the 10,6 ± 3.2 years in the ones without incontinence/soiling (p< 0,001). We found that the 5 cases of constipation arose in patients with TAB (p= 0, 044), and likewise all were operated under 1 year of age. CONCLUSION: Despite the well known benefits of the TERPT over the TAB, we found a greater degree of incontinence/soiling in the TERPT, which could be explained by a less follow up, since incontinence/soiling improves with age. On the other hand there is a higher rate of constipation in the TAB that lasts in time.

OBJETIVO: Analizar resultados funcionales de pacientes operados por enfermedad de Hirschsprung (EH). MATERIAL Y METODOS: Estudio retrospectivo de pacientes con EH (2000-2014). Se analizó técnica quirúrgica, edad diagnóstica y de tratamiento, cantidad de intestino resecado, complicaciones y su influencia sobre resultados funcionales. RESULTADOS: De los 44 diagnosticados con EH se operaron en nuestro centro 37. Varones 29 (78,4%). Con patología asociada 7 (18,9%), y 5 (13,5%) debutaron con enterocolitis. Edad media diagnóstica 1,04 (rango: 0,01-7,1 años) y de intervención 1,4 (0,3-9,3 años). A 17 (45,9%) se realizó descenso endorectal trans-anal (DERTA) y a 20 (54,1%) descenso trans-abdominal (DTA). Recibieron dilataciones postquirúrgicas 8 (21,6%). Los resultados funcionales se valoraron a una edad media de 9,6 (4,7-15,7 años) encontrando incontinencia/encopresis en 6/28 (21,4%) y estreñimiento en 5/28 (17,9%). El mayor índice de incontinencia/encopresis se presentó en los DERTA 41,7% vs 6,2% DTA (p= 0,036); sin embargo, la edad media al seguimiento en pacientes con incontinencia/encopresis fue menor 5,9 ± 1,3 años vs 10,6 ± 3,2 años en los que no la presentan (p< 0,001). Encontramos que los 5 casos de estreñimiento se presentaron en pacientes con DTA (p= 0,044) y, así mismo, todos operados ≤ 1 año de edad. CONCLUSIONES: A pesar de los ya comprobados beneficios del DERTA sobre el DTA, hemos encontrado un mayor grado de incontinencia/encopresis en el DERTA, que podría estar explicado por el menor tiempo de seguimiento, dado que la incontinencia/encopresis mejora con la edad. Por el contrario, hay un mayor índice de estreñimiento en el DTA que se prolonga en el tiempo.

Resultados funcionales en postoperados de enfermedad de Hirschsprung / Functional outcomes in postsurgery for Hirschsprung's disease

Objetivo. Analizar resultados funcionales de pacientes operados por enfermedad de Hirschsprung (EH). Material y métodos. Estudio retrospectivo de pacientes con EH (2000-2014). Se analizó técnica quirúrgica, edad diagnóstica y de tratamiento, cantidad de intestino resecado, complicaciones y su influencia sobre resultados funcionales. Resultados. De los 44 diagnosticados con EH se operaron en nuestro centro 37. Varones 29 (78,4%). Con patología asociada 7 (18,9%), y 5 (13,5%) debutaron con enterocolitis. Edad media diagnóstica 1,04 (rango: 0,01-7,1 años) y de intervención 1,4 (0,3-9,3 años). A 17 (45,9%) se realizó descenso endorectal trans-anal (DERTA) y a 20 (54,1%) descenso trans-abdominal (DTA). Recibieron dilataciones postquirúrgicas 8 (21,6%). Los resultados funcionales se valoraron a una edad media de 9,6 (4,7-15,7 años) encontrando incontinencia/encopresis en 6/28 (21,4%) y estreñimiento en 5/28 (17,9%). El mayor índice de incontinencia/encopresis se presentó en los DERTA 41,7% vs 6,2% DTA (p= 0,036); sin embargo, la edad media al seguimiento en pacientes con incontinencia/encopresis fue menor 5,9 ± 1,3 años vs 10,6 ± 3,2 años en los que no la presentan (p0,001). Encontramos que los 5 casos de estreñimiento se presentaron en pacientes con DTA (p= 0,044) y, así mismo, todos operados ≤ 1 año de edad. Conclusión. A pesar de los ya comprobados beneficios del DERTA sobre el DTA, hemos encontrado un mayor grado de incontinencia/encopresis en el DERTA, que podría estar explicado por el menor tiempo de seguimiento, dado que la incontinencia/encopresis mejora con la edad. Por el contrario, hay un mayor índice de estreñimiento en el DTA que se prolonga en el tiempo (AU)

Objective. To analyze functional outcomes of patients operated for Hirschsprung's disease (HD). Methods and materials. Retrospective study of patients with HD (2000-2014). We analyzed surgical technique, age at diagnostic and treatment, amount of resected bowel, complications and their influence on functional outcomes. Results. Of the 44 diagnosed with HD, 37 were operated in our center. Men 29 (78.4%). With associated pathology 7 (18.9%), and 5 (13.5%) made their debut with enterocolitis. Diagnostic average age 1.04 (0.0 to 7.1 years) and operation average age 1.4 (0.3 to 9.3 years). We did transanal endorectal pull-through (TERPT) in 17 (45.9%) patients and transabdominal approach (TAB) in 20 (54.1%). Received postoperative dilations 8 (21.6%) patients. Functional outcomes were evaluated at an average age of 9.6 (4.7-15.7years) incontinence/soiling were found in 6/28 (21.4%) and constipation in 5/28 (17.9%). The highest rate of incontinence/ soiling was present in 41.7 % TERPT vs. 6.2% TAB (p= 0,036). However, the average age at follow-up in patients with incontinence/soiling was 5.9 ± 1.3 years old, less than the 10,6 ± 3.2 years in the ones without incontinence/soiling (p< 0,001). We found that the 5 cases of constipation arose in patients with TAB (p= 0, 044), and likewise all were operated under 1 year of age. Conclusion. Despite the well known benefits of the TERPT over the TAB, we found a greater degree of incontinence/soiling in the TERPT, which could be explained by a less follow up, since incontinence/soiling improves with age. On the other hand there is a higher rate of constipation in the TAB that lasts in time (AU)

Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. METHODS: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used. All samples were formalin-fixed paraffin-embedded, selected and evaluated by a pathologist. For droplet digital PCR, 20 patients diagnosed with NSCLC at baseline or progression to different lines of TKI therapies were selected. Formalin-fixed paraffin-embedded blocks corresponding to either primary tumor or metastasis specimens were used for analysis. For single-cell analysis, orthotopically grown metastases were dissected from the brain of an athymic nu/nu mouse and cryopreserved at -80°C. RESULTS: In a brain metastasis lesion from a NSCLC patient presenting an EGFR T790M mutation, we detected MET gene amplification after prolonged treatment with osimertinib. Importantly, the combination of capmatinib (c-MET inhibitor) and afatinib (ErbB-1/2/4 inhibitor) completely suppressed tumor growth in mice orthotopically injected with cells derived from this brain metastasis. In those mice treated with capmatinib or afatinib as monotherapy, we observed the emergence of KRAS G12C clones. Single-cell gene expression analyses also revealed intratumor heterogeneity, indicating the presence of a KRAS-driven subclone. We also detected low-frequent KRAS G12C alleles in patients treated with various EGFR-TKIs. CONCLUSION: Acquired resistance to subsequent EGFR-TKI treatment lines in EGFR-mutant lung cancer patients may induce genetic plasticity. We assess the biological insights of tumor heterogeneity in an osimertinib-resistant tumor with acquired MET-amplification and propose new treatment strategies in this situation.

Immune-checkpoint inhibition in first-line treatment of advanced non-small cell lung cancer patients: Current status and future approaches.

Immune checkpoint inhibitors are considered standard second-line treatment in advanced non-small cell lung cancer patients. This strategy has also become standard in first-line setting for a subgroup of patients with strongly positive PD-L1 tumors; therefore, PD-L1 status might be considered a new biomarker that deserves upfront testing. New combinations of immune checkpoint inhibitors and with chemotherapy have been tested in first-line treatment. However, some questions remain unanswered such as the best treatment strategy or the real upfront efficacy of these therapeutic strategies in the whole lung cancer population. In this review we summarize the main results in the first-line setting of recent phase III trials with immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

[Intestinal stomas. Are they as simple as they seem?] / Enterostomías, ¿son tan simples como parecen?

OBJECTIVES: To examine the morbidity and mortality of the formation and closure of enterostomies. METHODS: Retrospective study between 2000-2014 of patients younger than 14 years old who underwent an enterostomy. We evaluated: surgical technique, underlying pathology, general and stoma complications, sex, age and weight at the time of formation. At the closure we evaluated: surgical technique, age, weight, hemoglobin, hematocrit and albumin, as well as complications. RESULTS: We performed 120 enterostomies in 114 patients: 69 (57.5%) colostomies, 43 (35.8%) ileostomies and 8 (6.7%) yeyunostomy. The most frequent causes were: anorectal malformation (45/69), necrotizing enterocolitis (24/43) and intestinal atresia (4/8) respectively. 39 (32.5%) complications related to the stoma (colostomy 21, Ileostomy 15, Yeyunostomy 3; p= 0.845), 11 (9.2%) required surgery (colostomy 8, Ileostomy 2, Yeyunostomy 1; p= 0.439), and 17 (14.2%) general complications (colostomy 9, Ileostomy 7, Yeyunostomy 1; p= 0.884). We found a higher rate of complications requiring surgery in loop enterostomy 8/38 (21.1%), separated 3/54 (5.3%) or double-barrel 0/25 (p= 0.007). We closed 96 (80%), presenting complications in 14; yeyunostomy 4/6 (66.7%), colostomies 5/59 (8.5%), ileostomies 5/31 (16.1%) (p= 0.001). Hematocrit and hemoglobin below age average, and albumin under normal values are associated with complications when closing enterostomies (p< 0.05). Six patients (25%) who didn't went to closure died as a result of the underlying pathology and 5 (20.8%) of other causes. CONCLUSION: The formation and closing of enterostomies remains a procedure with a high rate of complications. However, there are no clear risk factors, excepting the use of loop enterostomy and lower albumin, hemoglobin or hematocrit at the time of closure.

OBJETTIVO: Examinar la morbimortalidad de la realización y cierre de las enterostomías. MATERIAL Y METODOS: Estudio retrospectivo entre 2000-2014, de pacientes menores de 14 años a los que se les realizó una enterostomía. Evaluamos: técnica quirúrgica, patología base, complicaciones del estoma y generales, sexo, edad y peso al momento de la cirugía. Al cierre evaluamos: técnica quirúrgica, edad, peso, hemoglobina, hematocrito y albúmin, así como complicaciones. RESULTADOS: En 114 pacientes, realizamos 120 enterostomías: colostomías 69 (57,5%), ileostomías 43 (35,8%) y yeyunostomías 8 (6,7%); las causas más frecuentes para cada una: malformación ano-rectal (45/69), enterocolitis necrotizante (24/43) y atresia intestinal (4/8) respectivamente. Complicaciones relacionadas al estoma 39 (32,5%) (colostomía 21, ileostomía 15, yeyunostomía 3; p= 0,845), requirieron cirugía 11 (9,2%) (colostomía 8, ileostomía 2, yeyunostomía 1; p= 0,439), y complicaciones generales 17 (14,2%) (colostomía 9, ileostomía 7, yeyunostomía 1; p= 0,884). Encontrando mayor índice de complicaciones que requirieron cirugía en la enterostomía en asa 8/38 (21,1%), separada 3/54 (5,3%) o cañón 0/25 (p= 0,007). Cerramos 96 (80%), presentando complicaciones 14; yeyunostomías 4/6 (66,7%), colostomías 5/59 (8,5%), ileostomías 5/31 (16,1%) (p= 0,001). Se asocian a complicaciones del cierre hemoglobina y hematocrito por debajo de la media para la edad, y albúmina bajo valores normales (p< 0,05). De los pacientes no anastomosados, 6 (25%) fallecieron por patología base y 5 (20,8%) por otra causa. CONCLUSION: La elaboración y cierre de enterostomías sigue siendo un procedimiento con alto índice de complicaciones. Sin embargo, no existen factores de riesgo claros, a excepción del uso de la enterostomía en asa y de albúmina, hemoglobina y hematocrito bajos al cierre.

Enterostomías, ¿son tan simples como parecen? / Intestinal stomas, are they as simple as they seem?

Objetivo. Examinar la morbimortalidad de la realización y cierre de las enterostomías. Material y métodos. Estudio retrospectivo entre 2000-2014, de pacientes menores de 14 años a los que se les realizó una enterostomía. Evaluamos: técnica quirúrgica, patología base, complicaciones del estoma y generales, sexo, edad y peso al momento de la cirugía. Al cierre evaluamos: técnica quirúrgica, edad, peso, hemoglobina, hematocrito y albúmin, así como complicaciones. Resultados. En 114 pacientes, realizamos 120 enterostomías: colostomías 69 (57,5%), ileostomías 43 (35,8%) y yeyunostomías 8 (6,7%); las causas más frecuentes para cada una: malformación anorectal (45/69), enterocolitis necrotizante (24/43) y atresia intestinal (4/8) respectivamente. Complicaciones relacionadas al estoma 39 (32,5%) (colostomía 21, ileostomía 15, yeyunostomía 3; p= 0,845), requirieron cirugía 11 (9,2%) (colostomía 8, ileostomía 2, yeyunostomía 1; p= 0,439), y complicaciones generales 17 (14,2%) (colostomía 9, ileostomía 7, yeyunostomía 1; p= 0,884). Encontrando mayor índice de complicaciones que requirieron cirugía en la enterostomía en asa 8/38 (21,1%), separada 3/54 (5,3%) o cañón 0/25 (p= 0,007). Cerramos 96 (80%), presentando complicaciones 14; yeyunostomías 4/6 (66,7%), colostomías 5/59 (8,5%), ileostomías 5/31 (16,1%) (p= 0,001). Se asocian a complicaciones del cierre hemoglobina y hematocrito por debajo de la media para la edad, y albúmina bajo valores normales (p< 0,05). De los pacientes no anastomosados, 6 (25%) fallecieron por patología base y 5 (20,8%) por otra causa. Conclusión. La elaboración y cierre de enterostomías sigue siendo un procedimiento con alto índice de complicaciones. Sin embargo, no existen factores de riesgo claros, a excepción del uso de la enterostomía en asa y de albúmina, hemoglobina y hematocrito bajos al cierre

Objectives. To examine the morbidity and mortality of the formation and closure of enterostomies. Methods. Retrospective study between 2000-2014 of patients younger than 14 years old who underwent an enterostomy. We evaluated: surgical technique, underlying pathology, general and stoma complications, sex, age and weight at the time of formation. At the closure we evaluated: surgical technique, age, weight, hemoglobin, hematocrit and albumin, as well as complications. Results. We performed 120 enterostomies in 114 patients: 69 (57.5%) colostomies, 43 (35.8%) ileostomies and 8 (6.7%) yeyunostomy. The most frequent causes were: anorectal malformation (45/69), necrotizing enterocolitis (24/43) and intestinal atresia (4/8) respectively. 39 (32.5%) complications related to the stoma (colostomy 21, Ileostomy 15, Yeyunostomy 3; p= 0.845), 11 (9.2%) required surgery (colostomy 8, Ileostomy 2, Yeyunostomy 1; p= 0.439), and 17 (14.2%) general complications (colostomy 9, Ileostomy 7, Yeyunostomy 1; p= 0.884). We found a higher rate of complications requiring surgery in loop enterostomy 8/38 (21.1%), separated 3/54 (5.3%) or double-barrel 0/25 (p= 0.007). We closed 96 (80%), presenting complications in 14; yeyunostomy 4/6 (66.7%), colostomies 5/59 (8.5%), ileostomies 5/31 (16.1%) (p= 0.001). Hematocrit and hemoglobin below age average, and albumin under normal values are associated with complications when closing enterostomies (p< 0.05). Six patients (25%) who didn’t went to closure died as a result of the underlying pathology and 5 (20.8%) of other causes. Conclusion. The formation and closing of enterostomies remains a procedure with a high rate of complications. However, there are no clear risk factors, excepting the use of loop enterostomy and lower albumin, hemoglobin or hematocrit at the time of closure

Importancia de los tumores lipomatosos benignos en el niño como marcadores de anomalías estructurales y síndromes complejos. Experiencia en nuestro centro / Benign lipomatous tumors in children: markers of structural anomalies and complex syndromes. Our experience

Introducción: El lipoma es el tumor mesenquimatoso más frecuente entre los tumores de partes blandas. Su incidencia en la edad pediátrica es menor del 10%; sin embargo, estos tumores con frecuencia forman parte de síndromes complejos o son marcadores de anomalías estructurales subyacentes. Material y métodos: Estudio descriptivo restrospectivo de los tumores lipomatosos intervenidos en nuestro centro (2000-2014) en pacientes con edades comprendidas entre 0 y 15 años, y revisión bibliográfica con el objetivo de determinar las características epidemiológicas, su presentación clínica, su asociación con otras entidades clínicas complejas y su evolución posterior. Se excluyeron los pacientes con diagnóstico macroscópico de lipoma en los que el estudio anatomopatológico mostró lesiones de diferente estirpe. Resultados: Un total de 36 pacientes (un 47% mujeres y un 53% varones, con una media de edad de 7,9 años) presentaron tumores lipomatosos. El 75% eran lipomas únicos, cuya localización más frecuente era la extremidad inferior (29%). La localización lumbosacra se asoció a anomalías del tubo neural. En el 2,7% de los casos se manifestó como lipomatosis múltiple superficial; el 8,3% formaba parte de síndromes complejos y 1 caso presentó un lipoma profundo. En el 95% se realizó una resección completa. Los lipomas inguinocrurales, intramusculares o múltiples presentaban una mayor tendencia a la recidiva. Conclusiones: Los tumores adiposos son infrecuentes en los niños. La asociación a síndromes complejos o a una patología grave supone un porcentaje muy elevado con respecto a la población adulta. Es fundamental realizar una correcta anamnesis y una exploración para detectar las posibles anomalías asociadas y valorar la necesidad de efectuar pruebas de neuroimagen en las localizaciones craneal o lumbosacra (AU)

Introduction: Benign lipomas are the most frequent soft tissue tumors. In children, its incidence has been estimated at around 10% of mesenchymal tumors and they are frequently associated with complex syndromes or structural abnormalities. Material and methods: We conducted a descriptive retrospective study of the fatty tumors diagnosed and treated in our centre (2000-2014) in children (0-15 aged) and a literature review in order to determine their epidemiological characteristics, presentation, complex pathology associated, treatment and prognosis. Patients with pathology report showing different histological diagnosis are excluded. Results: 36 patients (47% females, 53% males, medium age 7.9 years) were diagnosed of fatty tumors. The 75% presented isolated lipomas, the most frequent location was the lower extremity (29%). Lumbosacral lipomas were associated with tube neural defects. The 2.7% presented multiple superficial lipomatosis, the 8.3% were associated with congenital complex syndromes and 1 case presented a deep mediastinal lipoma. Complete resection was performed in 95%. Inguinal location, intramuscular and multiple lipomatosis were associated with relapse. Conclusions: Fatty tumors are infrequent in children. A high percentage of patients present congenital syndromes or disease associated, which shows a higher proportion comparing with adults. A detailed anamnesis and physical exploration are mandatory to detect other defects and neuroimaging techniques must be considered in lumbosacral or craneal lipomas (AU)

Hipertrofia de labios menores. Un problema creciente en la adolescencia / Hypertrophy of labia minora. A growing problem in adolescence

Objetivo. La hipertrofia de labios menores en la adolescencia es una patología poco conocida. Ante la creciente demanda de pacientes con este problema, fue necesaria su inclusión en nuestra cartera de servicios. El objetivo del presente estudio es la valoración de los resultados estéticos y funcionales de la labioplastia mediante la resección simple lineal de los bordes labiales. Métodos. Revisamos a pacientes intervenidas por hipertrofia de labios menores. Evaluando resultados estéticos, funcionales y complicaciones quirúrgicas. Asimismo, realizamos una encuesta sobre el grado de satisfacción. Resultados. Intervenimos 16 pacientes con 28 labioplastias, indicadas por molestias con la vestimenta y el ejercicio. Se realizaron a una mediana de edad de 13,43 años (rango 11,25-14,31). Siendo bilaterales 11 (64,7%), izquierdos 4 (23,5%) y derechos 2 (11,8%). La mediana de estancia hospitalaria fue un día (rango 1-3). Se evidenció una complicación inmediata (3,57%) (dehiscencia parcial de la herida) y 2 (7,14%) tardías (granuloma en la cicatriz y recidiva), en una mediana de seguimiento de 1,58 años (rango 0,19-7,76). A la encuesta respondieron 13 pacientes, el 100% refirieron que las molestias preoperatorias estaban resueltas o mucho mejor; el 61,54% no indicó ninguna o muy pocas molestias postoperatorias (tirantez o dolor), siendo la mediana de tiempo de las molestias 5 días (rango 1-30). Sintieron una mejora de la autoestima el 69,23% y el 30,77% restante nunca presentaron problema al respecto. La mediana de grado de satisfacción global fue 8 (rango 7-10) y el 100% repetirían la cirugía. Conclusión. La labioplastia mediante resección simple en la adolescencia es una técnica efectiva con pocas complicaciones, y con un alto grado de satisfacción para las pacientes

Objective. Hypertrophy of labia minora in adolescence is a little known disease. However, the growing demand for the solution of this problem pushes us to include it in our clinical practice. We evaluated the aesthetic and functional results of labiaplasty using straight amputation of the protuberant tissue of the labial edges. Methods. Patients treated by hypertrophy of labia minora were reviewed. We evaluated the results of aesthetic, functional and surgical complications. A survey on the degree of satisfaction was also conducted. Results. We collected 16 patients with 28 labioplasty, indicated by discomfort with the clothing and exercise. They were performed at a median age of 13.43 years (range 11.25-14.31). Bilateral 11 (64.7%), left 4(23.5%) and rights 2 (11.8%). The median hospital stay was 1 day (range 1-3). There was evidence of immediate complications (partial dehiscence of the scar) in 1 (3.57%) patient and late complications in 2 (7.14%) patients (granuloma in the scar and recurrence), in a median follow up time of 1.58 years (range 0.19-7.76). The survey was answered by 13 patients. All of them said that preoperative discomfort was resolved. Postoperative discomfort (pain or straps) were nothing or very few in 61.54% and the median time of inconvenience was 5 days (range 1-30). They felt an improvement in self-esteem 69.23% and the 30.77% remaining never presented a problem about that. Median overall satisfaction was 8 (range 7-10) over 10, and the 100% of patients would repeat surgery. Conclusion. The labiaplasty by straight amputation in adolescence is an effective technique with few complications, and with a high degree of satisfaction for patients

El quiste tirogloso intratiroideo en el diagnóstico diferencial del nódulo tiroideo solitario: a propósito de 2 casos / The intra-thyroid thyroglossal cyst in the differential diagnosis of the solitary thyroid nodule: A presentation of 2 cases

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Valoración clínica de la incontinencia fecal en pacientes intervenidos de malformación anorrectal / Clinical assessment of fecal incontinence in patients with anorectal malformation surgery

Objetivos. Aportar nuestra experiencia en el manejo de las malformaciones anorrectales (MAR) y comparar dos escalas cuantitativas para la valoración clínica de la incontinencia fecal. Material y métodos. Revisamos los pacientes intervenidos de MAR con edades comprendidas entre los 3 y 15 años. Recogimos una serie de variables y evaluamos la incontinencia fecal mediante dos escalas: la de Holschneider y una utilizada previamente en nuestro Servicio, cuyos ítems se completaron mediante entrevista clínica. Resultados. Estudiamos 48 pacientes, 29 niños y 19 niñas. El 81% presentaba factores de buen pronóstico (grupo A) y el 19% de mal pronóstico (grupo B) según la clasificación de Peña. El tratamiento realizado fue la anorrectoplastia sagital posterior (ARPSP) en 32 pacientes, ARPSP más descenso vía abdominal en 3, descenso abdominal en 2 y anoplastia tipo "Cut-Back" en 14. No existieron diferencias significativas en la edad media de continencia (3,41 ± 1,80 años en grupo A vs 3,92 ± 1,07 en grupo B; p= 0,35). No encontramos diferencias significativas en la media de puntuación de incontinencia utilizando nuestra escala (17,57/20 en grupo A vs 14/20 en grupo B; p= 0,05), pero fue significativamente menor en el grupo B utilizando la de Holschneider (12,39/14 en grupo A vs 10,43/14 en grupo B; p= 0,04). En 16 pacientes se detectó estreñimiento; de ellos, la mitad presentó pérdidas por rebosamiento. Conclusiones. Nuestra escala penaliza el estreñimiento, por este motivo la puntuación media del grupo A fue menor y no se encontraron diferencias respecto al grupo B, contrariamente a lo ocurrido con la escala de Holschneider, por lo que podría resultar más precisa para valorar la incontinencia fecal de estos pacientes

Background/purpose. To review our management of anorectal malformations (ARM) and to compare two quantitative scales for clinical assessment of fecal incontinence. Material and methods. We reviewed all patients with ARM surgery who are currently 3 to 15 years old. Several variables were collected and fecal incontinence was evaluated using two scales: the Holschneider scale and one used previously in our Service, both were filled out through clinical interview. Results. 48 patients were studied, 29 males and 19 females. According to the Peña’s classification, 81% had good prognosis indicators (group A) and 19% had bad prognosis indicators (group B). Posterior sagittal anorectoplasty (PSARP) was performed in 32 patients, PSARP and abdominal approach in 3, abdomino-perineal pullthrough in 2, and a "Cut-back" anoplasty in 14 patients. There were not statistical significative differences in average age of continence between both groups. We found no significative differences on the average score of fecal incontinence between both groups using our scale (17.57/20 in group A vs 14/20 in group B; p= 0.05) but it was significantly lower in group B using the Holschneider scale (12.39/14 in group A vs 10.43/14; p= 0.04). Constipation was detected in 16 patients, half of whom had overflow pseudoincontinence. Conclusions. Our scale penalizes constipation, for this reason the average score of group A was lower and we didn’t find differences with respect to group B, contrary to what it happened using Holschneider’s scale, so we believe our scale could be more precise to evaluate fecal incontinence of these patients

[Clinical assessment of fecal incontinence in patients with anorectal malformation surgery]. / Valoración clínica de la incontinencia fecal en pacientes intervenidos de malformación anorrectal.

BACKGROUND/PURPOSE: To review our management of anorectal malformations (ARM) and to compare two quantitative scales for clinical assessment of fecal incontinence. MATERIAL AND METHODS: We reviewed all patients with ARM surgery who are currently 3 to 15 years old. Several variables were collected and fecal incontinence was evaluated using two scales: the Holschneider scale and one used previously in our Service, both were filled out through clinical interview. RESULTS: 48 patients were studied, 29 males and 19 females. According to the Peña's classification, 81% had good prognosis indicators (group A) and 19% had bad prognosis indicators (group B). Posterior sagittal anorectoplasty (PSARP) was performed in 32 patients, PSARP and abdominal approach in 3, abdomino-perineal pullthrough in 2, and a "Cut-back" anoplasty in 14 patients. There were not statistical significative differences in average age of continence between both groups. We found no significative differences on the average score of fecal incontinence between both groups using our scale (17.57/20 in group A vs 14/20 in group B; p= 0.05) but it was significantly lower in group B using the Holschneider scale (12.39/14 in group A vs 10.43/14; p= 0.04). Constipation was detected in 16 patients, half of whom had overflow pseudoincontinence. CONCLUSIONS: Our scale penalizes constipation, for this reason the average score of group A was lower and we didn't find differences with respect to group B, contrary to what it happened using Holschneider's scale, so we believe our scale could be more precise to evaluate fecal incontinence of these patients.

OBJETIVOS: Aportar nuestra experiencia en el manejo de las malformaciones anorrectales (MAR) y comparar dos escalas cuantitativas para la valoración clínica de la incontinencia fecal. MATERIAL Y METODOS: Revisamos los pacientes intervenidos de MAR con edades comprendidas entre los 3 y 15 años. Recogimos una serie de variables y evaluamos la incontinencia fecal mediante dos escalas: la de Holschneider y una utilizada previamente en nuestro Servicio, cuyos ítems se completaron mediante entrevista clínica. RESULTADOS: Estudiamos 48 pacientes, 29 niños y 19 niñas. El 81% presentaba factores de buen pronóstico (grupo A) y el 19% de mal pronóstico (grupo B) según la clasificación de Peña. El tratamiento realizado fue la anorrectoplastia sagital posterior (ARPSP) en 32 pacientes, ARPSP más descenso vía abdominal en 3, descenso abdominal en 2 y anoplastia tipo "Cut-Back" en 14. No existieron diferencias significativas en la edad media de continencia (3,41 ± 1,80 años en grupo A vs 3,92 ± 1,07 en grupo B; p= 0,35). No encontramos diferencias significativas en la media de puntuación de incontinencia utilizando nuestra escala (17,57/20 en grupo A vs 14/20 en grupo B; p= 0,05), pero fue significativamente menor en el grupo B utilizando la de Holschneider (12,39/14 en grupo A vs 10,43/14 en grupo B; p= 0,04). En 16 pacientes se detectó estreñimiento; de ellos, la mitad presentó pérdidas por rebosamiento. CONCLUSIONES: Nuestra escala penaliza el estreñimiento, por este motivo la puntuación media del grupo A fue menor y no se encontraron diferencias respecto al grupo B, contrariamente a lo ocurrido con la escala de Holschneider, por lo que podría resultar más precisa para valorar la incontinencia fecal de estos pacientes.

[Hypertrophy of labia minora. A growing problem in adolescence]. / Hipertrofia de labios menores. Un problema creciente en la adolescencia.

OBJECIVE: Hypertrophy of labia minora in adolescence is a little known disease. However, the growing demand for the solution of this problem pushes us to include it in our clinical practice. We evaluated the aesthetic and functional results of labiaplasty using straight amputation of the protuberant tissue of the labial edges. METHODS: Patients treated by hypertrophy of labia minora were reviewed. We evaluated the results of aesthetic, functional and surgical complications. A survey on the degree of satisfaction was also conducted. RESULTS: We collected 16 patients with 28 labioplasty, indicated by discomfort with the clothing and exercise. They were performed at a median age of 13.43 years (range 11.25-14.31). Bilateral 11 (64.7%), left 4 (23.5%) and rights 2 (11.8%). The median hospital stay was 1 day (range 1-3). There was evidence of immediate complications (partial dehiscence of the scar) in 1 (3.57%) patient and late complications in 2 (7.14%) patients (granuloma in the scar and recurrence), in a median follow up time of 1.58 years (range 0.19-7.76). The survey was answered by 13 patients. All of them said that preoperative discomfort was resolved. Postoperative discomfort (pain or straps) were nothing or very few in 61.54% and the median time of inconvenience was 5 days (range 1-30). They felt an improvement in self-esteem 69.23% and the 30.77% remaining never presented a problem about that. Median overall satisfaction was 8 (range 7-10) over 10, and the 100% of patients would repeat surgery. CONCLUSION: The labiaplasty by straight amputation in adolescence is an effective technique with few complications, and with a high degree of satisfaction for patients.

OBJETIVO: La hipertrofia de labios menores en la adolescencia es una patología poco conocida. Ante la creciente demanda de pacientes con este problema, fue necesaria su inclusión en nuestra cartera de servicios. El objetivo del presente estudio es la valoración de los resultados estéticos y funcionales de la labioplastia mediante la resección simple lineal de los bordes labiales. METODOS: Revisamos a pacientes intervenidas por hipertrofia de labios menores. Evaluando resultados estéticos, funcionales y complicaciones quirúrgicas. Asimismo, realizamos una encuesta sobre el grado de satisfacción. RESULTADOS: Intervenimos 16 pacientes con 28 labioplastias, indicadas por molestias con la vestimenta y el ejercicio. Se realizaron a una mediana de edad de 13,43 años (rango 11,25-14,31). Siendo bilaterales 11 (64,7%), izquierdos 4 (23,5%) y derechos 2 (11,8%). La mediana de estancia hospitalaria fue un día (rango 1-3). Se evidenció una complicación inmediata (3,57%) (dehiscencia parcial de la herida) y 2 (7,14%) tardías (granuloma en la cicatriz y recidiva), en una mediana de seguimiento de 1,58 años (rango 0,19-7,76). A la encuesta respondieron 13 pacientes, el 100% refirieron que las molestias preoperatorias estaban resueltas o mucho mejor; el 61,54% no indicó ninguna o muy pocas molestias postoperatorias (tirantez o dolor), siendo la mediana de tiempo de las molestias 5 días (rango 1-30). Sintieron una mejora de la autoestima el 69,23% y el 30,77% restante nunca presentaron problema al respecto. La mediana de grado de satisfacción global fue 8 (rango 7-10) y el 100% repetirían la cirugía. CONCLUSION: La labioplastia mediante resección simple en la adolescencia es una técnica efectiva con pocas complicaciones, y con un alto grado de satisfacción para las pacientes.

El nacimiento de la higiene dental y los dientes de Waterloo / No disponible

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Triada de Currarino: sus diferentes formas de presentación / Currarino triad: Different forms of presentation

Objetivos. Presentar nuestra experiencia en casos diagnosticados de síndrome de Currarino y sus diferentes formas de presentación. material y métodos. Caso 1: neoanata con diagnóstico prenatal por RM de mielomeningocele confirmado al nacimiento como lipomielomeningocele asociado a atresia ano-rectal alta con vascularización anómala del colon, agenesia parcial sacra y riñón en herradura. Caso 2: varón de 14 meses con clínica de estreñimiento y diagnóstico de estenosis anal, lipomeningocele presacro más teratoma y agenesia parcial sacra. Caso 3: varón de 8 meses con clínica de meningitis de repetición y diagnosticado de estenosis anal, meningocele anterior con fístula rectal y agenesia parcial sacra. Resultados. El caso 1 tras un descenso abdomino-perineal fallido por vascularización anómala es portadora actual de cecostomía y a los 3 años de vida presenta un buen control urinario y de la deambulación. El caso 2, con dos años de vida, evoluciona favorablemente con hábito intestinal normal tras extirpación del teratoma y meningocele más dilatación anal. El caso 3 precisó una colostomía tras extirpación del meningocele con fístula rectal por fístula recto-cutánea en el postoperatorio inmediato y derivación ventriculoperitoneal por hidrocefalia postmeningitis. Conclusiones. Según la bibliografía, la forma de presentación del síndrome de Currarino (SC) puede ser muy variada, siendo lo más frecuente el estreñimiento. La presentación más compleja y con alto índice de mortalidad (56%) es la meningitis de repetición debido a fístulas recto-meníngeas. La malformación ano-rectal más frecuente es la estenosis anal y malformaciones más complejas tienen un alto índice de incontinencia. Es un síndrome que precisa de manejo y seguimiento multidisciplinar (AU)

Background. We describe our experience in Currarino syndrome (CS) and our clinical findings. methods. Case 1: Newborn female with prenatal diagnosis of myelomeningocele which was confirmed at birth as a lipomyelomeningocele, associated with partial sacral agenesis, horseshoe kidney and complex anorectal malformation with colonic vascular anomaly. Case 2: A 14-month-old male with constipation. The physical examination detected an anal stricture and radiological findings of a presacral lipomeningocele plus teratoma and a partial sacral agenesis. Case 3:An 8-month-old male with recurrent meningitis associated with anterior sacral meningocele and rectal fistula. An anal stricture and hemisacrum were also demonstrated. Results. In case 1, an abdomino-perineal pull-through was performed but it failed because of her colonic vascular anomaly. Nowadays she is 3 years old and has a cecostomy, controls her micturition and is able to walk. Case 2 is two years old with satisfactory flow-up-after the teratoma and meningocele removal plus anal dilation. In case 3 a colostomy was necessary because after mass excision a recto-cutaneous fistula appeared during postoperative period. A ventriculoperitoneal valve implantation due to his hydrocephaly was also performed. Conclusions. The constipation is the most common symptom in the CS. Recurrent meningitis has a high mortality rate (56%) due to rectomeningeal fistula. The most common anorectal malformation is the anal stricture, and the more complex the malformation is, higher will the risk of incontinence be. The success of the management and follow-up is a multidisciplinary responsability (AU)

[Currarino triad: different forms of presentation]. / Triada de Currarino: sus diferentes formas de presentación.

BACKGROUND: We describe our experience in Currarino syndrome (CS) and our clinical findings. METHODS: Case 1: Newborn female with prenatal diagnosis of myelomeningocele which was confirmed at birth as a lipomyelomeningocele, associated with partial sacral agenesis, horseshoe kidney and complex anorectal malformation with colonic vascular anomaly. Case 2: A 14-month-old male with constipation. The physical examination detected an anal stricture and radiological findings of a presacral lipomeningocele plus teratoma and a partial sacral agenesis. Case 3: An 8-month-old male with recurrent meningitis associated with anterior sacral meningocele and rectal fistula. An anal stricture and hemisacrum were also demonstrated. RESULTS: In case 1, an abdomino-perineal pull-through was performed but it failed because of her colonic vascular anomaly. Nowadays she is 3 years old and has a cecostomy, controls her micturition and is able to walk. Case 2 is two years old with satisfactory flow-up-after the teratoma and meningocele removal plus anal dilation. In case 3 a colostomy was necessary because after mass excision a recto-cutaneous fistula appeared during postoperative period. A ventriculoperitoneal valve implantation due to his hydrocephaly was also performed. CONCLUSIONS: The constipation is the most common symptom in the CS. Recurrent meningitis has a high mortality rate (56%) due to rectomeningeal fistula. The most common anorectal malformation is the anal stricture, and the more complex the malformation is, higher will the risk of incontinence be. The success of the management and follow-up is a multidisciplinary responsability.

WT1 mutations may be a cause of severe renal failure due to nephroblastomatosis in Wilms' tumor patients.

Wilms' tumor suppressor gene (WT1) encodes a transcription factor required for normal development of the genitourinary system. Germline WT1 mutations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms' tumor. Here we report a 4-year-old male patient who presented with bilateral cryptorchidism, Wilms' tumor, nephroblastomatosis and renal failure without nephrotic proteinuria. Sequence analysis of the WT1 gene demonstrated a constitutional heterozygous nonsense mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc-finger 1. In the DNA of the tumor, we observed the same mutation in homo/hemizygosity. Given the requirement of WT1 for normal development, the WT1 mutation is likely to be responsible for the nephroblastomatosis and, in consequence, for the severe renal failure observed in our patient. This finding extends the spectrum of kidney diseases related to WT1 mutations and points to the need to screen for this gene in children with genitourinary abnormalities and Wilms' tumor because of the associated risk of nephroblastomatosis and renal failure in those carrying WT1 mutations.